ArticleHuman molecular genetics2016
PARK2 enhancement is able to compensate mitophagy alterations found in sporadic Alzheimer's disease.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
115 citing papers in PubMed, 3 syntheses or guidelines pooled it, 199 citations in OpenAlex.
- Mitochondrial quality control in neurodegenerative diseases: from molecular mechanisms to natural product therapies.Frontiers in physiology · 2025Pooled it
- Insights Into Parkin-Mediated Mitophagy in Alzheimer's Disease: A Systematic Review.Frontiers in aging neuroscience · 2021Pooled it
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Mitophagy in neuronal health and disease: from mechanisms to neurodegeneration.The Journal of clinical investigation · 2026Review
- The role of phospho-ubiquitin in mitochondrial health and diseases.The Journal of biological chemistry · 2026Review
- Mitochondrial Dysfunction in Alzheimer's Disease and Mitochondria-Targeted Therapeutics.Cells · 2026Review
- Mitophagy: A key regulator in the pathophysiology and treatment of spinal cord injury.Neural regeneration research · 2026Article
- The impact of exercise on brain mitochondrial health and its relevance to Alzheimer's disease.Brain and environment · 2026Article
- Article
- Mitochondrial dysfunction in Alzheimer's disease: connecting pathophysiology with neuroimaging.Frontiers in aging neuroscience · 2026Review
- Mitophagy in the pathogenesis and management of disease.Cell research · 2026Review
- The absence of Parkin in hTau mice leads to synaptic mitochondrial dysfunction, alterations to the synaptic proteome, and increased phosphorylated tau in the Hippocampus.Neurobiology of disease · 2025Article
- Review
- Mitochondrial Quality Control in Neurodegeneration and Cancer: A Common Denominator, Distinct Therapeutic Challenges.International journal of molecular sciences · 2025Review
- Therapeutic potential of melatonin-induced mitophagy in the pathogenesis of Alzheimer's disease.Inflammopharmacology · 2025Review
- Neuronal regulated cell death in aging-related neurodegenerative diseases: key pathways and therapeutic potentials.Neural regeneration research · 2025Article
- Mitophagy's impacts on cancer and neurodegenerative diseases: implications for future therapies.Journal of hematology & oncology · 2025Review
- Interconnections of insulin/IGF-1 signaling and autophagy abnormalities in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Molecular Regulation of SASP in Cellular Senescence: Therapeutic Implications and Translational Challenges.Cells · 2025Review
- Roles of Ubiquitin Ligases and Deubiquitylases in Alzheimer's Disease.Molecular neurobiology · 2025Review
55 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Mitochondrial anomalies have been previously reported in patients' brain and peripheral tissue, suggesting their relevance in sporadic Alzheimer's disease (AD). The present work evaluates mitochondrial function and recycling in human fibroblasts and brain biopsies. Functional studies using patients' skin fibroblasts showed slower mitochondrial membrane potential recovery after a mitochondrial insult together with alterations in lysosomes and autophagy, accompanied by an increase of oxidized and ubiquitinated proteins. Impairment in mitophagy has been proven in these cells due to diminished PARK2 and insufficient vesicle induction, accumulating depolarized mitochondria and PINK1. Augmented Δ1 PINK1 fragment levels suggest an inhibitory effect over PARK2 translocation to the mitochondria, causing the accumulation of activated PINK1. Moreover, the overexpression of PARK2 diminished ubiquitinated proteins accumulation, improves its targeting to mitochondria and potentiates autophagic vesicle synthesis. This allows the reversion of mitophagy failure reflected in the recovery of membrane potential and the decrease of PINK1 and mitochondria accumulation. Sporadic AD fibroblasts exhibited alterations similar to what it could be found in patients' hippocampal samples at early stages of the disease, where there was an accumulation of PINK1 and Δ1 PINK1 together with abnormally increased mitochondrial content. Our findings indicate that mitophagy alterations can be considered a new hallmark of sporadic AD and validate the use of fibroblasts for modelling this pathology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.