ArticleHuman molecular genetics2019
The landscape of Parkin variants reveals pathogenic mechanisms and therapeutic targets in Parkinson's disease.
Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 92 citations in OpenAlex.
- Pleiotropic effects for Parkin and LRRK2 in leprosy type-1 reactions and Parkinson's disease.Proceedings of the National Academy of Sciences of the United States of America · 2019Trial
- In vitro and in vivo rescue of dopaminergic neurons in Parkinson's disease models after Parkin gene therapy.Gene therapy · 2026Article
- The role of phospho-ubiquitin in mitochondrial health and diseases.The Journal of biological chemistry · 2026Review
- High molecular weight insoluble parkin in the substantia nigra of patients with idiopathic Parkinson's disease.NPJ Parkinson's disease · 2026Article
- MTFR1L is a cardiac antiaging factor for maintenance of mitochondrial homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- E3 ubiquitin ligases in neurodegenerative diseases.Military Medical Research · 2026Review
- Mitochondrial resilience: a convergent framework for pathogenesis and neuroprotection in Parkinson's disease.Frontiers in pharmacology · 2026Review
- Autophagy and mitophagy at the synapse and beyond: implications for learning, memory and neurological disorders.Autophagy · 2026Review
- Activation of endogenous PRKN by structural derepression is linked to increased turnover of the E3 ubiquitin ligase.Autophagy · 2025Article
- 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
- Inborn errors of canonical autophagy in neurodegenerative diseases.Human molecular genetics · 2025Review
- Progress in Disease-Modifying Therapies for Parkinson's Disease.Aging and disease · 2025Review
- The Juvenile Parkinson's Disease Mutation C212Y Impairs Mitochondrial Homeostasis in a Caenorhabditis elegans Model.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Canonical and alternate mechanisms that regulate ubiquitylation by the E3 ligase parkin.Biochemical Society transactions · 2025Review
- Autosomal Recessive Cerebellar Ataxia-27 Caused by a Novel Loss-of-Function Variant of Ganglioside-Induced Differentiation Associated Protein 2 in a Spanish Family.Neurology. Genetics · 2025Article
- Link between Parkinson's disease and melanoma: insights into the influence of theFrontiers in oncology · 2025Review
- Rare Copy Number Variants Intersecting Parkinson's-associated Genes in a Cohort of children With Autism Spectrum Disorders.Neuroscience insights · 2025Article
- Bidirectional Mendelian Randomization Analysis of the Association Between Mitochondrial Proteins and Neurodegenerative Diseases.Brain and behavior · 2025Article
- Cooperative Substructure and Energetics of Allosteric Regulation of the Catalytic Core of the E3 Ubiquitin Ligase Parkin by Phosphorylated Ubiquitin.Biomolecules · 2024Article
- Mitophagy in health and disease. Molecular mechanisms, regulatory pathways, and therapeutic implications.Apoptosis : an international journal on programmed cell death · 2024Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in Parkin (PARK2), which encodes an E3 ubiquitin ligase implicated in mitophagy, are the most common cause of early-onset Parkinson's disease (EOPD). Hundreds of naturally occurring Parkin variants have been reported, both in Parkinson's disease (PD) patient and population databases. However, the effects of the majority of these variants on the function of Parkin and in PD pathogenesis remain unknown. Here we develop a framework for classification of the pathogenicity of Parkin variants based on the integration of clinical and functional evidence-including measures of mitophagy and protein stability and predictive structural modeling-and assess 51 naturally occurring Parkin variants accordingly. Surprisingly, only a minority of Parkin variants, even among those previously associated with PD, disrupted Parkin function. Moreover, a few of these naturally occurring Parkin variants actually enhanced mitophagy. Interestingly, impaired mitophagy in several of the most common pathogenic Parkin variants could be rescued both by naturally occurring (p.V224A) and structure-guided designer (p.W403A; p.F146A) hyperactive Parkin variants. Together, the findings provide a coherent framework to classify Parkin variants based on pathogenicity and suggest that several pathogenic Parkin variants represent promising targets to stratify patients for genotype-specific drug design.
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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.