ArticleNeurobiology of disease2017
Loss of spatacsin function alters lysosomal lipid clearance leading to upper and lower motor neuron degeneration.
Article in Neurobiology of disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 64 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.
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.
Phase 2 Pharmacological Trial to Evaluate the Safety of Miglustat Administration in Subjects With Spastic Paraplegia 11 (TreatSPG11)
An Observational Study in Subjects With Spastic Paraplegia Type 11 Taking Trehalose
Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Pooled it
- Miglustat does not impact clinical progression in patients with spastic paraplegia type 11.Neurogenetics · 2025Trial
- Whole-exome sequencing reveals a novel frameshift and a recurrent nonsense SPG11 variant causing rare familial amyotrophic lateral sclerosis type 5 in two consanguineous Pakistani families.Molecular biology reports · 2026Article
- Hereditary spastic paraplegia (HSP) gene 11 (Spg11) attenuates lipid accumulation in myeloid cells and neuroinflammation in the midbrain without affecting α-synuclein pathology.Journal of neuroinflammation · 2026Article
- Microglial lipid droplets as therapeutic targets in age-related neurodegenerative diseases.npj aging · 2025Review
- Microglia and CD8+ T cell activation precede neuronal loss in a murine model of spastic paraplegia 15.The Journal of experimental medicine · 2025Article
- Article
- Deciphering distinct genetic risk factors for FTLD-TDP pathological subtypes via whole-genome sequencing.Nature communications · 2025Article
- Hereditary spastic paraplegia with thin corpus callosum and SPG11 mutation: A neuropathological evaluation.Neuropathology : official journal of the Japanese Society of Neuropathology · 2025Article
- Neurodevelopmental Implications Underpinning Hereditary Spastic Paraplegia.CNS neuroscience & therapeutics · 2025Review
- Transcriptomic analysis reinforces the implication of spatacsin in neuroinflammation and neurodevelopment.Scientific reports · 2025Article
- Endosomal traffic disorders: a driving force behind neurodegenerative diseases.Translational neurodegeneration · 2024Review
- Hereditary spastic paraparesis type 18 (SPG18): new ERLIN2 variants in a series of Italian patients, shedding light upon genetic and phenotypic variability.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- Unexpected complexity in the molecular diagnosis of spastic paraplegia 11.Molecular genetics & genomic medicine · 2024Article
- Pluripotent Stem Cells as a Preclinical Cellular Model for Studying Hereditary Spastic Paraplegias.International journal of molecular sciences · 2024Review
- Neuroinflammatory disease signatures in SPG11-related hereditary spastic paraplegia patients.Acta neuropathologica · 2024Article
- Clinically approved immunomodulators ameliorate behavioral changes in a mouse model of hereditary spastic paraplegia type 11.Frontiers in neuroscience · 2024Article
- Hereditary Spastic Paraplegia Type 11-Clinical, Genetic and Neuroimaging Characteristics.International journal of molecular sciences · 2023Article
- Liver-X-receptor agonists rescue axonal degeneration in SPG11-deficient neurons via regulating cholesterol trafficking.Neurobiology of disease · 2023Article
- Spatacsin regulates directionality of lysosome trafficking by promoting the degradation of its partner AP5Z1.PLoS biology · 2023Article
4 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
16 authors at 2 institutions in 2 countries.
Funding
Abstract
Mutations in SPG11 account for the most common form of autosomal recessive hereditary spastic paraplegia (HSP), characterized by a gait disorder associated with various brain alterations. Mutations in the same gene are also responsible for rare forms of Charcot-Marie-Tooth (CMT) disease and progressive juvenile-onset amyotrophic lateral sclerosis (ALS). To elucidate the physiopathological mechanisms underlying these human pathologies, we disrupted the Spg11 gene in mice by inserting stop codons in exon 32, mimicking the most frequent mutations found in patients. The Spg11 knockout mouse developed early-onset motor impairment and cognitive deficits. These behavioral deficits were associated with progressive brain atrophy with the loss of neurons in the primary motor cortex, cerebellum and hippocampus, as well as with accumulation of dystrophic axons in the corticospinal tract. Spinal motor neurons also degenerated and this was accompanied by fragmentation of neuromuscular junctions and muscle atrophy. This new Spg11 knockout mouse therefore recapitulates the full range of symptoms associated with SPG11 mutations observed in HSP, ALS and CMT patients. Examination of the cellular alterations observed in this model suggests that the loss of spatacsin leads to the accumulation of lipids in lysosomes by perturbing their clearance from these organelles. Altogether, our results link lysosomal dysfunction and lipid metabolism to neurodegeneration and pinpoint a critical role of spatacsin in lipid turnover.
Indexed as
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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.