Mitochondria-Division Inhibitor 1 Protects Against Amyloid-β induced Mitochondrial Fragmentation and Synaptic Damage in Alzheimer’s Disease
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The purpose our study was to determine the protective effects of mitochondria division inhibitor 1 (Mdivi1) in Alzheimer's disease (AD). Mdivi1 is hypothesized to reduce excessive fragmentation of mitochondria and mitochondrial dysfunction in AD neurons. Very little is known about whether Mdivi1 can confer protective effects in AD. In the present study, we sought to determine the protective effects of Mdivi1 against amyloid-β (Aβ)- and mitochondrial fission protein, dynamin-related protein 1 (Drp1)-induced excessive fragmentation of mitochondria in AD progression. We also studied preventive (Mdivi1+Aβ42) and intervention (Aβ42+Mdivi1) effects against Aβ42 in N2a cells. Using real-time RT-PCR and immunoblotting analysis, we measured mRNA and protein levels of mitochondrial dynamics, mitochondrial biogenesis, and synaptic genes. We also assessed mitochondrial function by measuring H2O2, lipid peroxidation, cytochrome oxidase activity, and mitochondrial ATP. MTT assays were used to assess the cell viability. Aβ42 was found to impair mitochondrial dynamics, lower mitochondrial biogenesis, lower synaptic activity, and lower mitochondrial function. On the contrary, Mdivi1 enhanced mitochondrial fusion activity, lowered fission machinery, and increased biogenesis and synaptic proteins. Mitochondrial function and cell viability were elevated in Mdivi1-treated cells. Interestingly, Mdivi1 pre- and post-treated cells treated with Aβ showed reduced mitochondrial dysfunction, and maintained cell viability, mitochondrial dynamics, mitochondrial biogenesis, and synaptic activity. The protective effects of Mdivi1 were stronger in N2a+Aβ42 pre-treated with Mdivi1, than in N2a+Aβ42 cells than Mdivi1 post-treated cells, indicating that Mdivi1 works better in prevention than treatment in AD like neurons.
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Decreased mitochondrial fragmentation was observed in vitro using N2a neuronal cells treated with Mdivi-1 prior to challenge with neurotoxic Aβ.
“Decreased mitochondrial fragmentation was observed in vitro using N2a neuronal cells treated with Mdivi-1 prior to challenge with neurotoxic Aβ [42].”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [42]
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Self-citation
- Authors
- Reddy, P. H., Manczak, M., & Yin, X.
- Affiliations
- Texas Tech University (US)
- Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, USA
- Texas Tech University Health Sciences Center (US)
- Corresponding author
- Reddy, P. Hemachandra
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2017-05-03
- Volume
- 58
- Issue
- 1
- Pages
- 147-162
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC5444307
- OpenAlex
- W2607143731
- Cited by
- 116
- References
- 58
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 14 · 2023: 10 · 2022: 14 · 2021: 20 · 2020: 21 · 2019: 8 · 2018: 9 · 2017: 2
- FWCI
- 4.47
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG042178, R01AG047812)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- Alzheimer's disease
- MeSH terms
- Adenosine Triphosphate, Animals, Electron Transport Complex IV, Drug Interactions, Hydrogen Peroxide, Mitochondria, Nerve Tissue Proteins, Neuroblastoma, Peptide Fragments, RNA, Messenger, Lipid Peroxidation, Gene Expression Regulation, Enzymologic, Amyloid beta-Peptides, Mitochondrial Proteins, Cell Line, Tumor, Mice, Quinazolinones, Mitochondrial Dynamics
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