Protective effects of a natural product, curcumin, against amyloid β induced mitochondrial and synaptic toxicities in Alzheimer's disease

P (Hemachandra) Reddy, Maria Manczak, Xiangling Yin, Mary Catharine Grady, Andrew Mitchell, Ramesh Kandimalla, Chandra Sekhar Kuruva

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The purpose of our study was to investigate the protective effects of a natural product-'curcumin'-in Alzheimer's disease (AD)-like neurons. Although much research has been done in AD, very little has been reported on the effects of curcumin on mitochondrial biogenesis, dynamics, function and synaptic activities. Therefore, the present study investigated the protective effects against amyloid β (Aβ) induced mitochondrial and synaptic toxicities. Using human neuroblastoma (SHSY5Y) cells, curcumin and Aβ, we studied the protective effects of curcumin against Aβ. Further, we also studied preventive (curcumin+Aβ) and intervention (Aβ+curcumin) effects of curcumin against Aβ in SHSY5Y cells. Using real time RT-PCR, immunoblotting and immunofluorescence analysis, we measured mRNA and protein levels of mitochondrial dynamics, mitochondrial biogenesis and synaptic genes. We also assessed mitochondrial function by measuring hydrogen peroxide, lipid peroxidation, cytochrome oxidase activity and mitochondrial ATP. Cell viability was studied using the MTT assay. Aβ was found to impair mitochondrial dynamics, reduce mitochondrial biogenesis and decrease synaptic activity and mitochondrial function. In contrast, curcumin enhanced mitochondrial fusion activity and reduced fission machinery, and increased biogenesis and synaptic proteins. Mitochondrial function and cell viability were elevated in curcumin treated cells. Interestingly, curcumin pre-and post-treated cells incubated with Aβ showed reduced mitochondrial dysfunction, and maintained cell viability and mitochondrial dynamics, mitochondrial biogenesis and synaptic activity. Further, the protective effects of curcumin were stronger in pretreated SHSY5Y cells than in post-treated cells, indicating that curcumin works better in prevention than treatment in AD-like neurons. Our findings suggest that curcumin is a promising drug molecule to treat AD patients.

Original languageEnglish (US)
Pages (from-to)1220-1234
Number of pages15
JournalJournal of Investigative Medicine
Volume64
Issue number8
DOIs
StatePublished - Dec 1 2016
Externally publishedYes

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Curcumin
Biological Products
Amyloid
Toxicity
Alzheimer Disease
Mitochondrial Dynamics
Cells
Organelle Biogenesis
Cell Survival
Neurons
Electron Transport Complex IV
Neuroblastoma
Immunoblotting
Hydrogen Peroxide
Lipid Peroxidation
Machinery
Fluorescent Antibody Technique
Real-Time Polymerase Chain Reaction
Assays
Proteins

Keywords

  • Aging
  • Alzheimer Disease
  • Antioxidants

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Protective effects of a natural product, curcumin, against amyloid β induced mitochondrial and synaptic toxicities in Alzheimer's disease. / Reddy, P (Hemachandra); Manczak, Maria; Yin, Xiangling; Grady, Mary Catharine; Mitchell, Andrew; Kandimalla, Ramesh; Kuruva, Chandra Sekhar.

In: Journal of Investigative Medicine, Vol. 64, No. 8, 01.12.2016, p. 1220-1234.

Research output: Contribution to journalArticle

Reddy, P (Hemachandra) ; Manczak, Maria ; Yin, Xiangling ; Grady, Mary Catharine ; Mitchell, Andrew ; Kandimalla, Ramesh ; Kuruva, Chandra Sekhar. / Protective effects of a natural product, curcumin, against amyloid β induced mitochondrial and synaptic toxicities in Alzheimer's disease. In: Journal of Investigative Medicine. 2016 ; Vol. 64, No. 8. pp. 1220-1234.
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