ArticleProceedings of the National Academy of Sciences of the United States of America2009
Membrane-associated farnesylated UCH-L1 promotes alpha-synuclein neurotoxicity and is a therapeutic target for Parkinson's disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 137 citations in OpenAlex.
- The Emerging Role of UCHL1 in Neurological and Musculoskeletal Diseases.Immunology and cell biology · 2026Review
- Targeting OTUD7A-HINT1 deubiquitination activates mTOR signaling for CNS regeneration.Cell death & disease · 2026Article
- Tightly Knotted Enzymes Inhibit Protein-Protein Aggregation.bioRxiv : the preprint server for biology · 2026Article
- Ketogenic diet regulates Uch-L1(C) to improve cerebral energy metabolism and cognitive function in Alzheimer's disease mice.European journal of histochemistry : EJH · 2026Article
- Statins and genetic inhibition of the mevalonate pathway activate an ATF3-STMN2 regenerative program.bioRxiv : the preprint server for biology · 2026Article
- Protein farnesylation: from molecular mechanisms to therapeutic targeting in cancer, aging, and beyond.Frontiers in pharmacology · 2026Review
- Autophagy-Lysosome Pathway in Multiple System Atrophy Pathogenesis: The Best Is Yet to Come.International journal of molecular sciences · 2025Review
- UCH-L1 in Alzheimer's Disease: A Crucial Player in Dementia-Associated Mechanisms.International journal of molecular sciences · 2025Review
- Article
- Roles of Ubiquitin Ligases and Deubiquitylases in Alzheimer's Disease.Molecular neurobiology · 2025Review
- Redox regulation, protein S-nitrosylation, and synapse loss in Alzheimer's and related dementias.Neuron · 2024Review
- Drug Repurposing for COVID-19 by Constructing a Comorbidity Network with Central Nervous System Disorders.International journal of molecular sciences · 2024Article
- Deficiency of UCHL1 results in insufficient decidualization accompanied by impaired dNK modulation and eventually miscarriage.Journal of translational medicine · 2024Article
- Systemic treatment with ubiquitin carboxy terminal hydrolase L1 TAT protein ameliorates axonal injury and reduces functional deficits after traumatic brain injury in mice.Experimental neurology · 2024Article
- Data-independent acquisition proteomics of cerebrospinal fluid implicates endoplasmic reticulum and inflammatory mechanisms in amyotrophic lateral sclerosis.Journal of neurochemistry · 2024Article
- Ubiquitin Carboxyl-Terminal Hydrolase L1 and Its Role in Parkinson's Disease.International journal of molecular sciences · 2024Review
- Regulation of Med1 protein by overexpression of BAP1 in breast cancer cells.Molecular & cellular oncology · 2024Article
- Role of UCHL1 in the pathogenesis of neurodegenerative diseases and brain injury.Ageing research reviews · 2023Review
- Review
- Marginalizing the genomic architecture to identify crosstalk across cancer and neurodegeneration.Frontiers in molecular neuroscience · 2023Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Ubiquitin C-terminal hydrolase-L1 (UCH-L1) is linked to Parkinson's disease (PD) and memory and is selectively expressed in neurons at high levels. Its expression pattern suggests a function distinct from that of its widely expressed homolog UCH-L3. We report here that, in contrast to UCH-L3, UCH-L1 exists in a membrane-associated form (UCH-L1(M)) in addition to the commonly studied soluble form. C-terminal farnesylation promotes the association of UCH-L1 with cellular membranes, including the endoplasmic reticulum. The amount of UCH-L1(M) in transfected cells is shown to correlate with the intracellular level of alpha-synuclein, a protein whose accumulation is associated with neurotoxicity and the development of PD. Reduction of UCH-L1(M) in cell culture models of alpha-synuclein toxicity by treatment with a farnesyltransferase inhibitor (FTI-277) reduces alpha-synuclein levels and increases cell viability. Proteasome function is not affected by UCH-L1(M), suggesting that it may negatively regulate the lysosomal degradation of alpha-synuclein. Therefore, inhibition of UCH-L1 farnesylation may be a therapeutic strategy for slowing the progression of PD and related synucleinopathies.
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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.