ArticleThe Journal of clinical investigation2012
Neurotoxin-induced ER stress in mouse dopaminergic neurons involves downregulation of TRPC1 and inhibition of AKT/mTOR signaling.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers.
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Who cites it
141 citing papers in PubMed, 238 citations in OpenAlex.
- Utility of Neuronal-Derived Exosomes to Examine Molecular Mechanisms That Affect Motor Function in Patients With Parkinson Disease: A Secondary Analysis of the Exenatide-PD Trial.JAMA neurology · 2019Trial
- Implant-derived titanium particles impair macrophage bacterial clearance via TRPC1 and lysosomal dysfunction.PNAS nexus · 2026Article
- Farnesol, a Dietary Sesquiterpene, Attenuates Rotenone-Induced Dopaminergic Neurodegeneration by Inhibiting Oxidative Stress, Inflammation, and Apoptosis via Mediation of Cell Signaling Pathways in Rats.International journal of molecular sciences · 2026Article
- Molecular Mechanisms of Dopaminergic Neuron Degeneration in Parkinson's Disease: A Comprehensive Review.Current neuropharmacology · 2026Review
- Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026Review
- Molecular architecture of the human TRPC1/C5 heteromeric channel.Nature communications · 2025Article
- Targeting the serotonergic system in the treatment of neurodegenerative diseases-emerging therapies and unmet challenges.Pharmacological reviews · 2025Review
- Intracerebellar upregulation of Rheb(S16H) ameliorates motor dysfunction in mice with SCA2.Acta pharmacologica Sinica · 2025Article
- Endoplasmic Reticulum Stress: Implications in Diseases.The protein journal · 2025Review
- Indole-3-acetic acid and chenodeoxycholic acid attenuate TLR4/NF-κB signaling and endoplasmic reticulum stress in valproic acid-induced neurotoxicity.Frontiers in pharmacology · 2025Article
- Unraveling the AKT/ERK cascade and its role in Parkinson disease.Archives of toxicology · 2024Review
- Targeting IGF1/IGF1r signaling relieve pain and autophagic dysfunction in NTG-induced chronic migraine model of mice.The journal of headache and pain · 2024Article
- Delivery of CDNF by AAV-mediated gene transfer protects dopamine neurons and regulates ER stress and inflammation in an acute MPTP mouse model of Parkinson's disease.Scientific reports · 2024Article
- Selective Assembly of TRPC Channels in the Rat Retina during Photoreceptor Degeneration.International journal of molecular sciences · 2024Article
- Electroacupuncture Improves Neuronal Damage and Mitochondrial Dysfunction Through the TRPC1 and SIRT1/AMPK Signaling Pathways to Alleviate Parkinson's Disease in Mice.Journal of molecular neuroscience : MN · 2024Article
- Advancements in Genetic and Biochemical Insights: Unraveling the Etiopathogenesis of Neurodegeneration in Parkinson's Disease.Biomolecules · 2024Review
- The Effects of Carvacrol on Transient Receptor Potential (TRP) Channels in an Animal Model of Parkinson's Disease.Neurotoxicity research · 2023Article
- Metformin-induced activation of CaJournal of translational autoimmunity · 2023Article
- Neuronal Store-Operated Calcium Channels.Molecular neurobiology · 2023Review
- Endoplasmic Reticulum Stress-Regulated Chaperones as a Serum Biomarker Panel for Parkinson's Disease.Molecular neurobiology · 2023Article
81 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
Abstract
Individuals with Parkinson's disease (PD) experience a progressive decline in motor function as a result of selective loss of dopaminergic (DA) neurons in the substantia nigra. The mechanism(s) underlying the loss of DA neurons is not known. Here, we show that a neurotoxin that causes a disease that mimics PD upon administration to mice, because it induces the selective loss of DA neurons in the substantia nigra, alters Ca²⁺ homeostasis and induces ER stress. In a human neuroblastoma cell line, we found that endogenous store-operated Ca²⁺ entry (SOCE), which is critical for maintaining ER Ca²⁺ levels, is dependent on transient receptor potential channel 1 (TRPC1) activity. Neurotoxin treatment decreased TRPC1 expression, TRPC1 interaction with the SOCE modulator stromal interaction molecule 1 (STIM1), and Ca²⁺ entry into the cells. Overexpression of functional TRPC1 protected against neurotoxin-induced loss of SOCE, the associated decrease in ER Ca²⁺ levels, and the resultant unfolded protein response (UPR). In contrast, silencing of TRPC1 or STIM1 increased the UPR. Furthermore, Ca²⁺ entry via TRPC1 activated the AKT pathway, which has a known role in neuroprotection. Consistent with these in vitro data, Trpc1⁻/⁻ mice had an increased UPR and a reduced number of DA neurons. Brain lysates of patients with PD also showed an increased UPR and decreased TRPC1 levels. Importantly, overexpression of TRPC1 in mice restored AKT/mTOR signaling and increased DA neuron survival following neurotoxin administration. Overall, these results suggest that TRPC1 is involved in regulating Ca²⁺ homeostasis and inhibiting the UPR and thus contributes to neuronal survival.
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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.