ArticleThe Journal of clinical investigation2018
Blocking p62-dependent SMN degradation ameliorates spinal muscular atrophy disease phenotypes.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Antisense oligonucleotides treatment uncovers differences in the modulation of dysregulated intracellular pathways in Spinal Muscular Atrophy motoneurons.Cell death & disease · 2026Article
- The survival motor neuron protein: structure, functions, stability, and therapeutic targeting.Frontiers in cellular neuroscience · 2026Review
- An induced pluripotent stem cell-based chemical genetic approach for studying spinal muscular atrophy.bioRxiv : the preprint server for biology · 2025Article
- An induced pluripotent stem cell-based chemical genetic approach for studying spinal muscular atrophy.Frontiers in neuroscience · 2025Article
- In Search of Spinal Muscular Atrophy Disease Modifiers.International journal of molecular sciences · 2024Review
- Significance of Programmed Cell Death Pathways in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Isogenic patient-derived organoids reveal early neurodevelopmental defects in spinal muscular atrophy initiation.Cell reports. Medicine · 2024Article
- Spinal Cord Organoids to Study Motor Neuron Development and Disease.Life (Basel, Switzerland) · 2023Review
- SMN post-translational modifications in spinal muscular atrophy.Frontiers in cellular neuroscience · 2023Review
- Autophagy in spinal muscular atrophy: from pathogenic mechanisms to therapeutic approaches.Frontiers in cellular neuroscience · 2023Review
- The role of autophagy-lysosomal pathway in motor neuron diseases.Biochemical Society transactions · 2022Review
- A combinatorial approach increases SMN level in SMA model mice.Human molecular genetics · 2022Article
- Hyper-SUMOylation of SMN induced by SENP2 deficiency decreases its stability and leads to spinal muscular atrophy-like pathology.Journal of molecular medicine (Berlin, Germany) · 2021Article
- Moments in autophagy and disease: Past and present.Molecular aspects of medicine · 2021Review
- Review
- Spinal Muscular Atrophy autophagy profile is tissue-dependent: differential regulation between muscle and motoneurons.Acta neuropathologica communications · 2021Article
- Cardiac Shock Wave Therapy Alleviates Hypoxia/Reoxygenation-Induced Myocardial Necroptosis by Modulating Autophagy.BioMed research international · 2021Article
- Regulatory networks between Polycomb complexes and non-coding RNAs in the central nervous system.Journal of molecular cell biology · 2020Review
- TRIM32, but not its muscular dystrophy-associated mutant, positively regulates and is targeted to autophagic degradation by p62/SQSTM1.Journal of cell science · 2019Article
- Mechanisms of exercise-induced survival motor neuron expression in the skeletal muscle of spinal muscular atrophy-like mice.The Journal of physiology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Spinal muscular atrophy (SMA), a degenerative motor neuron (MN) disease, caused by loss of functional survival of motor neuron (SMN) protein due to SMN1 gene mutations, is a leading cause of infant mortality. Increasing SMN levels ameliorates the disease phenotype and is unanimously accepted as a therapeutic approach for patients with SMA. The ubiquitin/proteasome system is known to regulate SMN protein levels; however, whether autophagy controls SMN levels remains poorly explored. Here, we show that SMN protein is degraded by autophagy. Pharmacological and genetic inhibition of autophagy increases SMN levels, while induction of autophagy decreases these levels. SMN degradation occurs via its interaction with the autophagy adapter p62 (also known as SQSTM1). We also show that SMA neurons display reduced autophagosome clearance, increased p62 and ubiquitinated proteins levels, and hyperactivated mTORC1 signaling. Importantly, reducing p62 levels markedly increases SMN and its binding partner gemin2, promotes MN survival, and extends lifespan in fly and mouse SMA models, revealing p62 as a potential new therapeutic target for the treatment of SMA.
Indexed as
Identifiers
What OpenQuestion holds
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.