ArticleJournal of Alzheimer's disease : JAD2021
PINK1 Activation Attenuates Impaired Neuronal-Like Differentiation and Synaptogenesis and Mitochondrial Dysfunction in Alzheimer's Disease Trans-Mitochondrial Cybrid Cells.
Article in Journal of Alzheimer's disease : JAD, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Research progress on the Sonic Hedgehog signaling pathway in the central nervous system: Novel insights.Neural regeneration research · 2026Article
- Role of mitochondria in neuronal function and survival in the enteric and central nervous systems.Cellular and molecular life sciences : CMLS · 2026Review
- Toward a Unified Framework in Molecular Neurobiology of Alzheimer's Disease: Revisiting the Pathophysiological Hypotheses.Molecular neurobiology · 2025Review
- PINK1-dependent NFKB signaling contributes to amyloid pathology in Alzheimer disease.Autophagy · 2025Article
- Potential Role of Membrane Contact Sites in the Dysregulation of the Crosstalk Between Mitochondria and Lysosomes in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- New cyclophilin D inhibitor rescues mitochondrial and cognitive function in Alzheimer's disease.Brain : a journal of neurology · 2024Article
- Mitochondria in Alzheimer's Disease Pathogenesis.Life (Basel, Switzerland) · 2024Review
- O-GlcNAc impacts mitophagy via the PINK1-dependent pathway.Frontiers in aging neuroscience · 2024Article
- Mitochondrial dysfunction and Alzheimer's disease: pathogenesis of mitochondrial transfer.Frontiers in aging neuroscience · 2024Review
- Study on the Pharmacological Mechanism of Icariin for the Treatment of Alzheimer's Disease Based on Network Pharmacology and Molecular Docking Techniques.Metabolites · 2023Article
- Glucocorticoid-driven mitochondrial damage stimulates Tau pathology.Brain : a journal of neurology · 2023Article
- The Role of Mitochondrial Dysfunction in Alzheimer's: Molecular Defects and Mitophagy-Enhancing Approaches.Life (Basel, Switzerland) · 2023Review
- Mitochondrial oxidative stress contributes to the pathological aggregation and accumulation of tau oligomers in Alzheimer's disease.Human molecular genetics · 2022Article
- A Review of ApoE4 Interference Targeting Mitophagy Molecular Pathways for Alzheimer's Disease.Frontiers in aging neuroscience · 2022Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMitochondrial dysfunction, bioenergetic deficit, and extensive oxidative stress underlie neuronal perturbation during the early stage of Alzheimer's disease (AD). Previously, we demonstrated that decreased PTEN-induced putative kinase 1 (PINK1) expression is associated with AD pathology in AD-affected human brains and AD mice.
objectiveIn the present study, we highlight the essential role of PINK1 in AD-relevant mitochondrial perturbation and neuronal malfunction.
methodsUsing trans-mitochondrial "cybrid" (cytoplasmic hybrid) neuronal cells, whose mitochondria are transferred from platelets of patients with sporadic AD, we observed the effect of PINK1 in neuronal-like differentiation and synaptogenesis and mitochondrial functions.
resultsIn AD cybrid cells, the downregulation of PINK1 is correlated to the alterations in mitochondrial morphology and function and deficit in neuronal-like differentiation. Restoring/increasing PINK1 by lentivirus transduction of PINK1 robustly attenuates mitochondrial defects and rescues neurite-like outgrowth. Importantly, defective PINK1 kinase activity fails to reverse these detrimental effects. Mechanistically, AD cybrid cells reveal a significant decrease in PINK1-dependent phosphorylated mitofusin (Mfn) 2, a key mitochondrial membrane protein that participates in mitochondrial fusion, and an insufficient autophagic activity for the clearance of dysfunctional mitochondria. Overexpression of PINK1, but not mutant PINK1 elevates phosphorylation of Mfn2 and autophagy signaling LC3-II. Accordingly, PINK1-overexpressed AD cybrids exhibit increases in mitochondrial length and density and suppressed reactive oxygen species. These results imply that activation of PINK1 protects against AD-affected mitochondrial dysfunction and impairment in neuronal maturation and differentiation.
conclusionPINK1-mediated mitophagy is important for maintaining mitochondrial health by clearance of dysfunctional mitochondria and therefore, improves energy homeostasis in AD.
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