Life Extension Magazine®

Husband and wife looking over papers after taking curcumin

Discovering Curcumin’s Brain Benefits

Curcumin fights leading brain disorders such as Alzheimer’s. New research findings show that curcumin can reduce anxiety and depression.

Scientifically reviewed by Dr. Gary Gonzalez, MD, in October 2024. Written by: Susan Lawrence.

Curcumin is a potent anti-inflammatory herb that has been demonstrated to protect against a host of degenerative conditions.1-9

Its role in protecting brain health is now taking the scientific world by storm.

Researchers are finding that curcumin can reduce anxiety/depression, promote neurite growth and induce brain plasticity.

Curcumin has been shown, in preclinical and animal studies, to promote the activity of brain-derived neurotropic factor (BDNF), a vital signaling factor that promotes the growth and strengthening of nerve networks vital to retaining cognitive and memory skills.10-16

Clinical and laboratory data show that curcumin prevents or reverses underlying features of today’s leading age-related brain conditions: Alzheimer’s, Parkinson’s, stroke, and brain cancer.

Curcumin Fights Leading Brain Disorders

Curcumin Fights Leading Brain Disorders  

Five crippling conditions account for a majority of the diseases that impact the brain and its function in aging Americans. These include, in order of their prevalence:

• Major depression (more than 15 million adults)

• Alzheimer’s disease (about 5.5 million)

• Parkinson’s disease (up to 1 million)

• Stroke (nearly 800,000 new cases/year)

• Brain cancer (nearly 80,000 new cases/year).17-21

These diverse and complex conditions share an important relationship, i.e. oxidative stress and inflammation.

Curcumin is well known for its anti-inflammatory and oxidative stress-fighting properties.22 More recently, curcumin has been found to favorably affect two critical processes that are at the core of learning and memory.

As a result of these properties, curcumin has been shown to have potent neuroprotective properties in the five leading brain disorders suffered by aging Americans.

What You Need to Know
Curcumin Promotes Brain Health

Curcumin Promotes Brain Health

  • Curcumin, long recognized for its ability to fight both oxidative stress and inflammation, has recently emerged as a leading brain health-promoting supplement.
  • Curcumin stimulates production of an essential growth factor, BDNF, that promotes new connections (neuronal plasticity) between brain cells.
  • Curcumin has also been shown in several preclinical studies to enhance outgrowth of neurites, nerve-cell projections that later develop into new cell-to-cell connections that facilitate plasticity.
  • Lab and clinical studies are already showing curcumin’s brain health-promoting properties, including encouraging results in depression, Alzheimer’s, Parkinson’s, stroke, and even brain tumors.
  • There’s no healthy aging without a healthy brain, so brain-protecting curcumin should be on every serious person’s “A-list” of essential supplements.

Depression

Researchers have discovered that major depression is associated with inflammation, oxidative stress, and microscopic-level brain-cell damage.23,24

These findings radically change our understanding of the causes and potential treatment of depression. Because of curcumin’s unique anti-stress and anti-inflammatory properties, scientists are now exploring it as a novel antidepressant.25

Animal studies going back nearly five years have shown that curcumin supplementation reduces depressive-like behaviors in established models of depression. More recently, studies in depressed humans are now confirming these results.

For example, taking 1,000 mg a day of a bioavailable curcumin has been found to be more effective than placebo at improving mood-related symptoms on standard depression scales.26,27 It was particularly effective in people with atypical depression, a variant of major depression that is often accompanied by weight gain, increased appetite, and lethargy.27,28

At the same 1,000 mg/day dose, curcumin enhanced with bioperine reduced the symptoms of anxiety among a group of obese subjects with depression and anxiety.29

In addition to these clinical benefits, research has shown that curcumin influences several salivary, urinary, and blood biomarkers of oxidative stress and inflammation.30

By mid-2017, there was enough data on curcumin’s impact on depression to warrant a meta-analysis.25 That study, which included six clinical trials and 377 patients in total, confirmed yet again that curcumin effectively reduced depression as measured by standardized depression scores. Three of those studies also reported significant antianxiety effects.25

No adverse events were reported in any of the trials, contrasting sharply with modern antidepressant drugs, which have side effects such as agitation, weight gain, insomnia, sexual problems, and increased suicidal tendencies.31

Alzheimer’s Disease

Alzheimer’s disease is the leading cause of dementia. Despite its prevalence, there is still no effective drug treatment.17,32,33

Promising studies are emerging on natural treatments for Alzheimer’s, and curcumin is a leading star.

In a study published in 2016, researchers gave older adults 1,500 mg of a specially-formulated curcumin supplement with enhanced bioavailability for 12 months. At six months of the study, the placebo group experienced a decline in cognitive function. There was no such drop in curcumin-supplemented subjects—an example of curcumin’s ability to protect the brain against cognitive decline.34

Clues as to why curcumin was so effective can be found in an earlier study in which taking just 80 mg of curcumin per day for four weeks led to lower blood triglycerides and adhesion molecules involved in vascular disease, along with higher levels of catalase, a natural protective enzyme.35 Importantly, subjects taking curcumin also had lower blood levels of beta-amyloid plaque, the toxic, nerve cell-damaging protein that is characteristic of Alzheimer’s brains.

These findings demonstrate some of the many ways that curcumin is capable of protecting against cognitive decline and neurodegeneration.

Animal studies reveal that curcumin works in four key ways to protect against Alzheimer’s.

First, Alzheimer’s patients often have abnormal insulin signaling pathways.36 Curcumin helps to normalize those pathways—a protective action that results in improved cognitive function, spatial learning, and memory.37,38

Another feature of Alzheimer’s is the loss of synapses,39 critical connections between nerve cells where signals are transmitted. Studies in mice show that supplementing with curcumin nearly eliminated abnormal synapses, while also improving synaptic numbers and structure. This led to improvements in spatial learning and memory.32,40

Loss of synapses—and in fact of entire brain cells—is largely triggered by the oxidation and inflammation that occur when beta-amyloid plaque builds up in the brain. Curcumin not only reduces brain inflammation caused by beta-amyloid plaque, but can also reverse its toxic impact on brain cells.41,42

Finally, curcumin inhibits the enzyme acetylcholinesterase, which helps boost levels of the neurotransmitter acetylcholine in synapses.43 This is the mechanism by which several Alzheimer’s drugs work.

Parkinson’s Disease

Parkinson’s Disease  

Parkinson’s severely impairs movement and balance, and carries a high risk of dementia.44,45 Like Alzheimer’s, Parkinson’s is driven by toxic protein accumulation, inflammation, and selective loss of dopamine-producing brain cells.46-48

These driving forces suggest that curcumin can function as a powerful ally against this brain-robbing disease—and studies are starting to back that up.

The first indications of curcumin’s protective effects were seen in laboratory studies. In these studies, toxic chemicals are often used to induce Parkinson’s-like symptoms in cell culture. But when these cells were pretreated with curcumin, they were completely protected against such toxicity.47

A similar model of Parkinson’s showed that curcumin enhanced cell survival, reduced cell death by apoptosis, and increased mitochondrial function—all important actions that provide both new life and renewed energy to afflicted cells.49

Studies in animal models of Parkinson’s have confirmed the observations made in laboratory studies.

For example, Parkinson’s disease can cause a reduction in the ability to experience pleasure (called anhedonia).50 This may include a loss of interest in eating, which can lead to undesired weight loss. In one rat study, curcumin supplementation increased healthy body weight of animals with Parkinson’s, while also reversing the disease-induced anhedonia.51

That same study showed that curcumin reduced the behavioral manifestations of Parkinson’s, while increasing amounts of the neurotransmitter dopamine. Increasing dopamine is critical, since it is the loss of dopamine that causes the lack of motor control associated with the disease.52

When researchers examined the animals’ brains directly, they found reduced damage in the memory-intensive hippocampal area of the brain,53 a powerful indicator of curcumin’s ability to protect the very structure of the brain.

A similar study in mice receiving curcumin also demonstrated improvements in behavior and mitochondrial function, with reduced oxidative damage to brain cells, compared with untreated animals.54

Strokes

An ischemic stroke occurs when blood flow is cut off to part of the brain, leaving brain cells inflamed and dying in its wake.55,56

Following stroke treatment to reopen an occluded cerebral artery, the inflammation and oxidative damage that results from the sudden return of blood can produce a process known as ischemia-reperfusion injury.57

Curcumin may help combat this type of injury, which means it could help minimize the damage caused by the stroke.

To test the effects of curcumin in rats, scientists gave the animals curcumin daily both before and after inducing a stroke. The treated animals showed significant increases in markers of cell restoration, an indication of improved healing after the acute stroke. They also had reduced oxidative damage during the reperfusion phase.58,59 Most remarkably, curcumin supplementation significantly reduced the behavioral effects of the stroke, while improving neurological scores.58

During stroke-induced brain cell injury, there is an increase in inflammation as the tissue heals.

Giving curcumin to the rats before they had a stroke was found to reduce the inflammation and mitochondrial dysfunction that typically occurs during the post-reperfusion phase of a stroke.60

Curcumin also shrank the size of the infarcted (cell death) zone in this study,60 and significantly reduces tissue swelling characteristic of the post-stroke state.61 Much of these effects, evident hours after the acute stroke, resulted from reductions in inflammatory signaling molecules.60

Overall, these studies show that taking curcumin as a protective measure could significantly reduce any damage caused by the stroke.

Brain Tumors

Despite their relatively low prevalence, brain tumors remain among the most-feared of clinical conditions.18

Curcumin is showing early signs of success in fighting brain tumors, especially the deadliest kind, glioblastomas.62 These tumors are highly aggressive and have an extremely poor prognosis. Average survival is just 15 months following diagnosis, and virtually no one survives past two years.63-65

Curcumin has several modes of action against cancer, including gliomas. Most promising is its ability to target cancer stem cells.6,62-64 These cells are resistant to radiation and chemotherapy.6,66,67

Curcumin has been shown to reduce cancer stem-cell survival and sensitize them to chemotherapy, making tumors more vulnerable to treatment.6,66,67

When applied directly to human brain-cancer cells in culture, curcumin induced cell death. It worked in two important ways: First, through inducing apoptosis (programmed cell death), and second, through destruction of the cells, within 72 hours of treatment.68

Curcumin also causes cell-cycle arrest, essentially “freezing” malignant cells into one phase of their replicative cycle. This makes it impossible for these aggressive cells to continue to multiply.69

A recent meta-analysis of 19 lab and five animal glioblastoma studies also demonstrated that cells and animals treated with curcumin lived longer than the control group.63 This is especially noteworthy considering the poor prognosis of this type of brain cancer.

Human studies are urgently needed as glioblastoma alone will be diagnosed in about 12,000 Americans this year.18

Curcumin Improves Critical Brain Connections

Curcumin Improves Critical Brain Connections  

Cognition, memory, spatial orientation, facial recognition, learning—all depend on intact brain structure and function.

We’ve seen that curcumin’s ability to combat inflammation and oxidative stress makes it a powerful ally for our brain health. A 2017 study uncovered another mechanism behind curcumin’s neuroprotective and cognition-enhancing properties: It promotes brain-cell plasticity.12

Neuronal plasticity is the degree to which connections between individual brain cells (neurons) can be made, broken, and remade rapidly.70 This allows us to stay in touch with the constant changes in environment, knowledge, and emotions. The ability to make these connections quickly—thousands of times faster than the fastest computer—is what underlies learning, memory, and cognition.

A major factor in supporting neuronal plasticity is the ability to produce neurites, which are tiny projections emanating from brain cells.71-73 Neurites form branches called dendrites, which connect our neurons. It is via these synaptic connections where nerve signals are transmitted.

Preclinical experiments have demonstrated impaired neurite outgrowth in models of neurodegenerative disease, depression, and stroke. This lack of ability to form connections between brain cells contributes substantially to impaired plasticity—and ultimately to weakened cognition, memory, and learning skills.74-79

This new knowledge about improving connectivity between brain cells is what makes curcumin so attractive to researchers.

Curcumin promotes vigorous neurite outgrowth and enhances neuronal plasticity.12,80-87 Even more encouraging is the fact that in these studies, curcumin administration resulted in the formation of new brain cells. This effect improved memory and increased cognitive function.12,84

These effects have been shown to counteract – and even reverse – the harmful effects of chronic stress and even brain injury on cognition, memory, learning, and plasticity.85,87

How It Works

How It Works  

Curcumin’s remarkable ability to enhance neurite outgrowth (and therefore, neuronal plasticity), comes from its ability to regulate a unique biochemical signaling molecule called brain-derived neurotrophic factor (BDNF).12-16

BDNF promotes neurite outgrowth, promotes brain-cell survival, and boosts synaptic plasticity—all of which help to build and maintain the neuronal circuits that let us learn, think, and remember.88,89 In essence, it’s what allows us to exist as individual humans.

It was only in late 2016 and early 2017 that scientists began to appreciate how powerfully curcumin promotes production and activation of BDNF in brain tissue.12-16

Piecing these studies together gives us a nearly-complete picture of how curcumin produces dramatic neuroprotective effects that contribute to improvements in age-related brain disorders.

Curcumin’s unique ability to upregulate BDNF secretion results in greater neurite outgrowth and, subsequently, improved brain plasticity—the very connections that are necessary to preserve cognition and memory.

Statistics on the Leading Brain Disorders in America
Brain Disorders

The following conditions lead the pack in threatening cognitive function, memory, and performance among older American adults, listed in order of prevalence.

Depression and Anxiety20

  • Major depression is the leading cause of disability in the US for ages 15-44, with a median onset age of 33.
  • Depression affects 6.7% of the US adult population (more than 15 million American adults) each year.
  • Depression is more prevalent in women than in men.
  • Anxiety disorders are the most common mental illness in America, afflicting 18% of the population, or about 40 million US adults.

Alzheimer’s Disease17

  • About 5.5 million Americans were living with Alzheimer’s dementia in 2017, 96% of whom are 65 or older.
  • Ten percent of those over 65 have Alzheimer’s dementia.
  • Alzheimer’s disease is the sixth leading cause of death among US adults.
  • One in three seniors dies with Alzheimer’s or another form of dementia.

Parkinson’s Disease21

  • About a million Americans live with Parkinson’s disease.
  • About 60,000 new cases of Parkinson’s are diagnosed each year in the US.
  • The incidence of Parkinson’s rises with age, but about 4% of sufferers are diagnosed before age 50.
  • Men develop Parkinson’s disease about 1.5 times as often as do women.

Stroke19

  • Approximately 795,000 Americans have a stroke each year.
  • Three out of four of those strokes are first-time events.
  • Strokes kill nearly 130,000 people every year, or one in 20 deaths, making it the number five cause of death in the US.
  • Most strokes (87%) are classified as being ischemic, in which blood flow is cut off to part of the brain, leaving cells inflamed and dying in its wake. Most other strokes are hemorrhagic, meaning that bleeding occurs into brain tissue, with much the same effect.

Brain Tumors18

  • About 80,000 new cases of primary brain tumors are diagnosed annually, with about one-third of these being malignant cancers.
  • Nearly 700,000 Americans are living with primary brain tumors (“primary” means originating in the brain, and excludes metastases from other cancers that end up in the brain).
  • The median age at diagnosis for all brain tumors is 59.
  • Glioblastomas are the most aggressive and malignant brain tumors, and are estimated to be diagnosed in more than 12,000 Americans annually.

Summary

Curcumin  

Healthy aging requires a healthy brain. The brain and its blood vessels are vulnerable to the same inflammation and oxidative stress that endanger blood vessels and other vital structures throughout the body.

Research is revealing that these same factors are involved in mental depression, neurodegeneration, stroke, and even brain cancer.

Curcumin is showing promise in battling all five of the leading age-related threats to brain health.

Curcumin’s multitargeted properties intervene in a host of critical factors involved in neurodegeneration, helping to preserve youthful cognition, memory, and learning.

An explosion of data reveals a unique property to curcumin’s brain health-promoting properties: It stimulates the production of BDNF, which promotes new connections (plasticity) between brain cells.

Lab studies demonstrate curcumin’s ability to promote neurite outgrowth and neuronal plasticity.

Curcumin already has a reputation as a broad-spectrum, health-promoting nutrient. It’s time to add it to responsible brain-health supplementation regimens.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

References

  1. Wongcharoen W, Jai-Aue S, Phrommintikul A, et al. Effects of curcuminoids on frequency of acute myocardial infarction after coronary artery bypass grafting. Am J Cardiol. 2012;110(1):40-4.
  2. Chuengsamarn S, Rattanamongkolgul S, Luechapudiporn R, et al. Curcumin extract for prevention of type 2 diabetes. Diabetes Care. 2012;35(11):2121-7.
  3. Deguchi A. Curcumin targets in inflammation and cancer. Endocr Metab Immune Disord Drug Targets. 2015;15(2):88-96.
  4. Fajardo AM, Piazza GA. Chemoprevention in gastrointestinal physiology and disease. Anti-inflammatory approaches for colorectal cancer chemoprevention. Am J Physiol Gastrointest Liver Physiol. 2015;309(2):G59-70.
  5. Qiao H, Fang D, Chen J, et al. Orally delivered polycurcumin responsive to bacterial reduction for targeted therapy of inflammatory bowel disease. Drug Deliv. 2017;24(1):233-42.
  6. Ramasamy TS, Ayob AZ, Myint HH, et al. Targeting colorectal cancer stem cells using curcumin and curcumin analogues: insights into the mechanism of the therapeutic efficacy. Cancer Cell Int. 2015;15:96.
  7. Sreedhar R, Arumugam S, Thandavarayan RA, et al. Curcumin as a therapeutic agent in the chemoprevention of inflammatory bowel disease. Drug Discov Today. 2016;21(5):843-9.
  8. Vallianou NG, Evangelopoulos A, Schizas N, et al. Potential anticancer properties and mechanisms of action of curcumin. Anticancer Res. 2015;35(2):645-51.
  9. Verma V. Relationship and interactions of curcumin with radiation therapy. World J Clin Oncol. 2016;7(3):275-83.
  10. Lee J, Duan W, Mattson MP. Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. J Neurochem. 2002;82(6):1367-75.
  11. Yamada K, Mizuno M, Nabeshima T. Role for brain-derived neurotrophic factor in learning and memory. Life Sci. 2002;70(7):735-44.
  12. Choi GY, Kim HB, Hwang ES, et al. Curcumin Alters Neural Plasticity and Viability of Intact Hippocampal Circuits and Attenuates Behavioral Despair and COX-2 Expression in Chronically Stressed Rats. Mediators Inflamm. 2017;2017:6280925.
  13. Wu X, Chen H, Huang C, et al. Curcumin attenuates surgery-induced cognitive dysfunction in aged mice. Metab Brain Dis. 2017;32(3):789-98.
  14. Motaghinejad M, Motevalian M, Fatima S, et al. The Neuroprotective Effect of Curcumin Against Nicotine-Induced Neurotoxicity is Mediated by CREB-BDNF Signaling Pathway. Neurochem Res. 2017.
  15. Motaghinejad M, Motevalian M, Fatima S, et al. Curcumin confers neuroprotection against alcohol-induced hippocampal neurodegeneration via CREB-BDNF pathway in rats. Biomed Pharmacother. 2017;87:721-40.
  16. Srivastava P, Dhuriya YK, Gupta R, et al. Protective Effect of Curcumin by Modulating BDNF/DARPP32/CREB in Arsenic-Induced Alterations in Dopaminergic Signaling in Rat Corpus Striatum. Mol Neurobiol. 2016.
  17. Available at: http://www.alz.org/facts/. Accessed 8 July, 2017.
  18. Available at: http://www.abta.org/about-us/news/brain-tumor-statistics/. Accessed 8 July, 2017.
  19. Available at: http://www.strokeassociation.org/STROKEORG/AboutStroke/Impact-of-Stroke-Stroke-statistics_UCM_310728_Article.jsp#.WdMEf0zMyis. Accessed 8 July, 2017.
  20. Available at: https://www.adaa.org/about-adaa/press-room/facts-statistics. Accessed 8 July, 2017.
  21. Available at: http://www.pdf.org/parkinson_statistics. Accessed 8 July, 2017.
  22. He Y, Yue Y, Zheng X, et al. Curcumin, inflammation, and chronic diseases: how are they linked? Molecules. 2015;20(5):9183-213.
  23. Black CN, Bot M, Scheffer PG, et al. Is depression associated with increased oxidative stress? A systematic review and meta-analysis. Psychoneuroendocrinology. 2015;51:164-75.
  24. Tizabi Y, Hurley LL, Qualls Z, et al. Relevance of the anti-inflammatory properties of curcumin in neurodegenerative diseases and depression. Molecules. 2014;19(12):20864-79.
  25. Ng QX, Koh SSH, Chan HW, et al. Clinical Use of Curcumin in Depression: A Meta-Analysis. J Am Med Dir Assoc. 2017;18(6):503-8.
  26. Lopresti AL, Drummond PD. Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study. J Affect Disord. 2017;207:188-96.
  27. Lopresti AL, Maes M, Maker GL, et al. Curcumin for the treatment of major depression: a randomised, double-blind, placebo controlled study. J Affect Disord. 2014;167:368-75.
  28. Available at: https://www.webmd.com/depression/guide/atypical-depression. Accessed October 10, 2017.
  29. Esmaily H, Sahebkar A, Iranshahi M, et al. An investigation of the effects of curcumin on anxiety and depression in obese individuals: A randomized controlled trial. Chin J Integr Med. 2015;21(5):332-8.
  30. Lopresti AL, Maes M, Meddens MJ, et al. Curcumin and major depression: a randomised, double-blind, placebo-controlled trial investigating the potential of peripheral biomarkers to predict treatment response and antidepressant mechanisms of change. Eur Neuropsychopharmacol. 2015;25(1):38-50.
  31. Available at: https://www.webmd.com/depression/features/coping-with-side-effects-of-depression-treatment. Accessed October 10, 2017.
  32. Zheng K, Dai X, Xiao N, et al. Curcumin Ameliorates Memory Decline via Inhibiting BACE1 Expression and beta-Amyloid Pathology in 5xFAD Transgenic Mice. Mol Neurobiol. 2017;54(3):1967-77.
  33. Available at: http://www.alz.org/alzheimers_disease_what_is_alzheimers.asp. Accessed October 10, 2017.
  34. Rainey-Smith SR, Brown BM, Sohrabi HR, et al. Curcumin and cognition: a randomised, placebo-controlled, double-blind study of community-dwelling older adults. Br J Nutr. 2016;115(12):2106-13.
  35. DiSilvestro RA, Joseph E, Zhao S, et al. Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people. Nutr J. 2012;11:79.
  36. Ribe EM, Lovestone S. Insulin signalling in Alzheimer’s disease and diabetes: from epidemiology to molecular links. J Intern Med. 2016;280(5):430-42.
  37. Feng HL, Dang HZ, Fan H, et al. Curcumin ameliorates insulin signalling pathway in brain of Alzheimer’s disease transgenic mice. Int J Immunopathol Pharmacol. 2016;29(4):734-41.
  38. Wang P, Su C, Feng H, et al. Curcumin regulates insulin pathways and glucose metabolism in the brains of APPswe/PS1dE9 mice. Int J Immunopathol Pharmacol. 2017;30(1):25-43.
  39. Lefort R. Reversing synapse loss in Alzheimer’s disease: Rho-guanosine triphosphatases and insights from other brain disorders. Neurotherapeutics. 2015;12(1):19-28.
  40. He Y, Wang P, Wei P, et al. Effects of curcumin on synapses in APPswe/PS1dE9 mice. Int J Immunopathol Pharmacol. 2016;29(2):217-25.
  41. Fan CD, Li Y, Fu XT, et al. Reversal of Beta-Amyloid-Induced Neurotoxicity in PC12 Cells by Curcumin, the Important Role of ROS-Mediated Signaling and ERK Pathway. Cell Mol Neurobiol. 2017;37(2):211-22.
  42. Liu ZJ, Li ZH, Liu L, et al. Curcumin Attenuates Beta-Amyloid-Induced Neuroinflammation via Activation of Peroxisome Proliferator-Activated Receptor-Gamma Function in a Rat Model of Alzheimer’s Disease. Front Pharmacol. 2016;7:261.
  43. Akinyemi AJ, Oboh G, Fadaka AO, et al. Curcumin administration suppress acetylcholinesterase gene expression in cadmium treated rats. Neurotoxicology. 2017;62:75-9.
  44. Available at: http://www.pdf.org/about_pd. Accessed October 10, 2017.
  45. Available at: http://www.alz.org/dementia/parkinsons-disease-symptoms.asp. Accessed October 10, 2017.
  46. Erustes AG, Stefani FY, Terashima JY, et al. Overexpression of alpha-synuclein in an astrocyte cell line promotes autophagy inhibition and apoptosis. J Neurosci Res. 2017.
  47. Qualls Z, Brown D, Ramlochansingh C, et al. Protective effects of curcumin against rotenone and salsolinol-induced toxicity: implications for Parkinson’s disease. Neurotox Res. 2014;25(1):81-9.
  48. Tufekci KU, Meuwissen R, Genc S, et al. Inflammation in Parkinson’s disease. Adv Protein Chem Struct Biol. 2012;88:69-132.
  49. van der Merwe C, van Dyk HC, Engelbrecht L, et al. Curcumin Rescues a PINK1 Knock Down SH-SY5Y Cellular Model of Parkinson’s Disease from Mitochondrial Dysfunction and Cell Death. Mol Neurobiol. 2017;54(4):2752-62.
  50. Loas G, Krystkowiak P, Godefroy O. Anhedonia in Parkinson’s disease: an overview. J Neuropsychiatry Clin Neurosci. 2012;24(4): 444-51.
  51. Yang J, Song S, Li J, et al. Neuroprotective effect of curcumin on hippocampal injury in 6-OHDA-induced Parkinson’s disease rat. Pathol Res Pract. 2014;210(6):357-62.
  52. Available at: https://www.ncbi.nlm.nih.gov/books/NBK6271/. Accessed October 10, 2017.
  53. Riedel G, Micheau J. Function of the hippocampus in memory formation: desperately seeking resolution. Prog Neuropsychopharmacol Biol Psychiatry. 2001;25(4):835-53.
  54. Khatri DK, Juvekar AR. Neuroprotective effect of curcumin as evinced by abrogation of rotenone-induced motor deficits, oxidative and mitochondrial dysfunctions in mouse model of Parkinson’s disease. Pharmacol Biochem Behav. 2016;150-151:39-47.
  55. Wang Q, Tang XN, Yenari MA. The inflammatory response in stroke. J Neuroimmunol. 2007;184(1-2):53-68.
  56. Available at: http://www.strokeassociation.org/STROKEORG/AboutStroke/TypesofStroke/IschemicClots/Ischemic-Strokes-Clots_UCM_310939_Article.jsp#.WdmGYltSwkI. Accessed October 10, 2017.
  57. Pan J, Konstas AA, Bateman B, et al. Reperfusion injury following cerebral ischemia: pathophysiology, MR imaging, and potential therapies. Neuroradiology. 2007;49(2):93-102.
  58. Liu S, Cao Y, Qu M, et al. Curcumin protects against stroke and increases levels of Notch intracellular domain. Neurol Res. 2016;38(6):553-9.
  59. Jia G, Tan B, Ma J, et al. Prdx6 Upregulation by Curcumin Attenuates Ischemic Oxidative Damage via SP1 in Rats after Stroke. Biomed Res Int. 2017;2017:6597401.
  60. Miao Y, Zhao S, Gao Y, et al. Curcumin pretreatment attenuates inflammation and mitochondrial dysfunction in experimental stroke: The possible role of Sirt1 signaling. Brain Res Bull. 2016;121:9-15.
  61. Zhang Y, Yan Y, Cao Y, et al. Potential therapeutic and protective effect of curcumin against stroke in the male albino stroke-induced model rats. Life Sci. 2017;183:45-9.
  62. Sordillo LA, Sordillo PP, Helson L. Curcumin for the Treatment of Glioblastoma. Anticancer Res. 2015;35(12):6373-8.
  63. Rodriguez GA, Shah AH, Gersey ZC, et al. Investigating the therapeutic role and molecular biology of curcumin as a treatment for glioblastoma. Ther Adv Med Oncol. 2016;8(4):248-60.
  64. Gersey ZC, Rodriguez GA, Barbarite E, et al. Curcumin decreases malignant characteristics of glioblastoma stem cells via induction of reactive oxygen species. BMC Cancer. 2017;17(1):99.
  65. Alifieris C, Trafalis DT. Glioblastoma multiforme: Pathogenesis and treatment. Pharmacol Ther. 2015;152:63-82.
  66. James MI, Iwuji C, Irving G, et al. Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal liver metastases, and is clinically safe and tolerable in combination with FOLFOX chemotherapy. Cancer Lett. 2015;364(2):135-41.
  67. Wu L, Guo L, Liang Y, et al. Curcumin suppresses stem-like traits of lung cancer cells via inhibiting the JAK2/STAT3 signaling pathway. Oncol Rep. 2015;34(6):3311-7.
  68. Alexandru O, Georgescu AM, Ene L, et al. The effect of curcumin on low-passage glioblastoma cells in vitro. J Cancer Res Ther. 2016;12(2):1025-32.
  69. Cheng C, Jiao JT, Qian Y, et al. Curcumin induces G2/M arrest and triggers apoptosis via FoxO1 signaling in U87 human glioma cells. Mol Med Rep. 2016;13(5):3763-70.
  70. Mahncke HW, Bronstone A, Merzenich MM. Brain plasticity and functional losses in the aged: scientific bases for a novel intervention. Prog Brain Res. 2006;157:81-109.
  71. Mingorance-Le Meur A. Internal regulation of neurite plasticity: A general model. Commun Integr Biol. 2009;2(4):318-20.
  72. Wainwright SR, Galea LA. The neural plasticity theory of depression: assessing the roles of adult neurogenesis and PSA-NCAM within the hippocampus. Neural Plast. 2013;2013:805497.
  73. Kurup N, Jin Y. Neural circuit rewiring: insights from DD synapse remodeling. Worm. 2016;5(1):e1129486.
  74. Nam KN, Mounier A, Wolfe CM, et al. Effect of high fat diet on phenotype, brain transcriptome and lipidome in Alzheimer’s model mice. Sci Rep. 2017;7(1):4307.
  75. Fujita K, Motoki K, Tagawa K, et al. HMGB1, a pathogenic molecule that induces neurite degeneration via TLR4-MARCKS, is a potential therapeutic target for Alzheimer’s disease. Sci Rep. 2016;6:31895.
  76. Schwab AJ, Ebert AD. Neurite Aggregation and Calcium Dysfunction in iPSC-Derived Sensory Neurons with Parkinson’s Disease-Related LRRK2 G2019S Mutation. Stem Cell Reports. 2015;5(6):1039-52.
  77. Uchida Y, Gomi F. The role of calsyntenin-3 in dystrophic neurite formation in Alzheimer’s disease brain. Geriatr Gerontol Int. 2016;16 Suppl 1:43-50.
  78. Hoyo-Becerra C, Schlaak JF, Hermann DM. Insights from interferon-alpha-related depression for the pathogenesis of depression associated with inflammation. Brain Behav Immun. 2014;42: 222-31.
  79. Huang X, Sun J, Zhao T, et al. Loss of NB-3 aggravates cerebral ischemia by impairing neuron survival and neurite growth. Stroke. 2011;42(10):2910-6.
  80. Dikmen M. Comparison of the Effects of Curcumin and RG108 on NGF-Induced PC-12 Adh Cell Differentiation and Neurite Outgrowth. J Med Food. 2017;20(4):376-84.
  81. Dikshit P, Goswami A, Mishra A, et al. Curcumin induces stress response, neurite outgrowth and prevent NF-kappaB activation by inhibiting the proteasome function. Neurotox Res. 2006;9(1):29-37.
  82. Lu Z, Shen Y, Wang T, et al. Curcumin promotes neurite outgrowth via reggie-1/flotillin-2 in cortical neurons. Neurosci Lett. 2014;559:7-12.
  83. Mendonca LM, da Silva Machado C, Teixeira CC, et al. Curcumin reduces cisplatin-induced neurotoxicity in NGF-differentiated PC12 cells. Neurotoxicology. 2013;34:205-11.
  84. Dong S, Zeng Q, Mitchell ES, et al. Curcumin enhances neurogenesis and cognition in aged rats: implications for transcriptional interactions related to growth and synaptic plasticity. PLoS One. 2012;7(2):e31211.
  85. Xu Y, Lin D, Li S, et al. Curcumin reverses impaired cognition and neuronal plasticity induced by chronic stress. Neuropharmacology. 2009;57(4):463-71.
  86. Wu A, Ying Z, Gomez-Pinilla F. Dietary curcumin counteracts the outcome of traumatic brain injury on oxidative stress, synaptic plasticity, and cognition. Exp Neurol. 2006;197(2):309-17.
  87. Zhang L, Luo J, Zhang M, et al. Effects of curcumin on chronic, unpredictable, mild, stress-induced depressive-like behaviour and structural plasticity in the lateral amygdala of rats. Int J Neuropsychopharmacol. 2014;17(5):793-806.
  88. Yuan Q, Sun L, Yu H, et al. Human microvascular endothelial cell promotes the development of dorsal root ganglion neurons via BDNF pathway in a co-culture system. Biosci Biotechnol Biochem. 2017;81(7):1335-42.
  89. Mizoguchi Y, Monji A. Microglial Intracellular Ca2+ Signaling in Synaptic Development and its Alterations in Neurodevelopmental Disorders. Front Cell Neurosci. 2017;11:69.