ArticleAnnals of clinical and translational neurology2016
Absence of UCHL 1 function leads to selective motor neuropathy.
Article in Annals of clinical and translational neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 38 citations in OpenAlex.
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- The relevance of combined testing of cerebrospinal fluid glial fibrillary acidic protein and ubiquitin C-terminal hydrolase L1 in multiple sclerosis and peripheral neuropathy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
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- Roles of Neuronal Protein Kinase Cε on Endoplasmic Reticulum Stress and Autophagic Formation in Diabetic Neuropathy.Molecular neurobiology · 2024Article
- Discovery of Biomarkers for Amyotrophic Lateral Sclerosis from Human Cerebrospinal Fluid Using Mass-Spectrometry-Based Proteomics.Biomedicines · 2023Article
- Role of UCHL1 in the pathogenesis of neurodegenerative diseases and brain injury.Ageing research reviews · 2023Review
- Neuronal models of TDP-43 proteinopathy display reduced axonal translation, increased oxidative stress, and defective exocytosis.Frontiers in cellular neuroscience · 2023Article
- Upper motor neurons are a target for gene therapy and UCHL1 is necessary and sufficient to improve cellular integrity of diseased upper motor neurons.Gene therapy · 2022Article
- Article
- SARS-CoV-2 Papain-Like Protease Potential Inhibitors-In Silico Quantitative Assessment.International journal of molecular sciences · 2021Article
- Behr syndrome and hypertrophic cardiomyopathy in a family with a novel UCHL1 deletion.Journal of neurology · 2020Article
- The Ubiquitin Proteasome System in Neuromuscular Disorders: Moving Beyond Movement.International journal of molecular sciences · 2020Review
- UCHL1 from serum and CSF is a candidate biomarker for amyotrophic lateral sclerosis.Annals of clinical and translational neurology · 2020Article
- The Electrophysiological Determinants of Corticospinal Motor Neuron Vulnerability in ALS.Frontiers in molecular neuroscience · 2020Article
- Neurodegenerative Diseases - Is Metabolic Deficiency the Root Cause?Frontiers in neuroscience · 2020Review
- Complexity of Generating Mouse Models to Study the Upper Motor Neurons: Let Us Shift Focus from Mice to Neurons.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveThe aim of this study was to investigate the role of ubiquitin C-terminal hydrolase-L1 (UCHL1) for motor neuron circuitry and especially in spinal motor neuron (SMN) health, function, and connectivity.
methodsSince mutations in UCHL1 gene leads to motor dysfunction in patients, we investigated the role of UCHL1 on SMN survival, axon health, and connectivity with the muscle, by employing molecular and cellular marker expression analysis and electrophysiological recordings, in healthy wild-type and Uchl1 (nm3419) (UCHL1-/-) mice, which lack all UCHL1 function.
resultsThere is pure motor neuropathy with selective degeneration of the motor, but not sensory axons in the absence of UCHL1 function. Neuromuscular junctions (NMJ) are impaired in muscle groups that are innervated by slow-twitch or fast-twitch SMN. However, unlike corticospinal motor neurons, SMN cell bodies remain intact with no signs of elevated endoplasmic reticulum (ER) stress.
interpretationPresence of NMJ defects and progressive retrograde axonal degeneration in the absence of major SMN soma loss suggest that defining pathology as a function of neuron number is misleading and that upper and lower motor neurons utilize UCHL1 function in different cellular events. In line with findings in patients with mutations in UCHL1 gene, our results suggest a unique role of UCHL1, especially for motor neuron circuitry. SMN require UCHL1 to maintain NMJ and motor axon health, and that observed motor dysfunction in the absence of UCHL1 is not due to SMN loss, but mostly due to disintegrated circuitry.
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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.