ArticleNature chemical biology2008
Novel targets for Huntington's disease in an mTOR-independent autophagy pathway.
Article in Nature chemical biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 418 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
418 citing papers in PubMed, 1 synthesis or guideline pooled it, 781 citations in OpenAlex.
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- Carbonic anhydrase inhibition ameliorates tau toxicity via enhanced tau secretion.Nature chemical biology · 2025Article
- Differential response of neurons to autophagy modulation in Huntington's disease.Autophagy reports · 2025Article
- Proteostasis disruption and lipid dyshomeostasis in neurodegeneration: exploring common druggable targets across sporadic and monogenic disorders.Frontiers in molecular neuroscience · 2025Review
- Niraparib perturbs autophagosome-lysosome fusion in pancreatic ductal adenocarcinoma and exhibits anticancer potential against gemcitabine-resistant PDAC.Translational oncology · 2025Article
- Autophagy-NADFrontiers in molecular biosciences · 2025Review
- Involvement of Autophagic Machinery in Neuropathogenesis: Targeting and Relevant Methods of Detection.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Brief and Diverse Excitotoxic Insults Increase the Neuronal Nuclear Membrane Permeability in the Neonatal Brain, Resulting in Neuronal Dysfunction and Cell Death.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
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- Excessive STAU1 condensate drives mTOR translation and autophagy dysfunction in neurodegeneration.The Journal of cell biology · 2024Article
- Exploring the Link Between Autophagy-Lysosomal Dysfunction and Early Heterotopic Ossification in Tendons.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
358 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Autophagy is a major clearance route for intracellular aggregate-prone proteins causing diseases such as Huntington's disease. Autophagy induction with the mTOR inhibitor rapamycin accelerates clearance of these toxic substrates. As rapamycin has nontrivial side effects, we screened FDA-approved drugs to identify new autophagy-inducing pathways. We found that L-type Ca2+ channel antagonists, the K+ATP channel opener minoxidil, and the G(i) signaling activator clonidine induce autophagy. These drugs revealed a cyclical mTOR-independent pathway regulating autophagy, in which cAMP regulates IP3 levels, influencing calpain activity, which completes the cycle by cleaving and activating G(s)alpha, which regulates cAMP levels. This pathway has numerous potential points where autophagy can be induced, and we provide proof of principle for therapeutic relevance in Huntington's disease using mammalian cell, fly and zebrafish models. Our data also suggest that insults that elevate intracytosolic Ca2+ (like excitotoxicity) inhibit autophagy, thus retarding clearance of aggregate-prone proteins.
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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.