A Proposed Mechanism for Neurodegeneration in Movement Disorders Characterized by Metal Dyshomeostasis and Oxidative Stress
| Autor: | Benjamin G. Trist, Dominic J. Hare, Kay L. Double |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Movement disorders animal diseases Clinical Biochemistry SOD1 Disease Biochemistry Superoxide dismutase 03 medical and health sciences 0302 clinical medicine Superoxide Dismutase-1 Drug Discovery medicine Animals Homeostasis Humans Amyotrophic lateral sclerosis Molecular Biology Pharmacology Movement Disorders biology Mechanism (biology) Neurodegeneration nutritional and metabolic diseases medicine.disease nervous system diseases Oxidative Stress 030104 developmental biology nervous system Metals Mutation biology.protein Molecular Medicine medicine.symptom Neuron death Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Cell chemical biology. 25(7) |
| ISSN: | 2451-9448 |
| Popis: | © 2018 Elsevier Ltd Shared molecular pathologies between distinct neurodegenerative disorders offer unique opportunities to identify common mechanisms of neuron death, and apply lessons learned from one disease to another. Neurotoxic superoxide dismutase 1 (SOD1) proteinopathy in SOD1-associated familial amyotrophic lateral sclerosis (fALS) is recapitulated in idiopathic Parkinson disease (PD), suggesting that these two phenotypically distinct disorders share an etiological pathway, and tractable therapeutic target(s). Despite 25 years of research, the molecular determinants underlying SOD1 misfolding and toxicity in fALS remain poorly understood. The absence of SOD1 mutations in PD highlights mounting evidence that SOD1 mutations are not the sole cause of SOD1 protein misfolding occasioning oligomerization and toxicity, reinforcing the importance of non-genetic factors, including protein metallation and post-translational modification in determining SOD1 stability and function. We propose that these non-genetic factors underlie the misfolding and dysfunction of SOD1 and other proteins in both PD and fALS, constituting a shared and tractable pathway to neurodegeneration. Trist et al. propose a shared etiological pathway in Parkinson disease and SOD1-associated familial amyotrophic lateral sclerosis, whereby concomitant changes in cellular copper and oxidative stress within dying neurons contribute to the dysfunction of specific proteins that are essential for maintaining neuronal health, including superoxide dismutase 1. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|