ReviewNeurobiology of disease2021
Lysosome dysfunction as a cause of neurodegenerative diseases: Lessons from frontotemporal dementia and amyotrophic lateral sclerosis.
Review in Neurobiology of disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers.
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Who cites it
153 citing papers in PubMed, 232 citations in OpenAlex.
- Lysosomal dysfunction in neurodegenerative disease.Nature reviews. Neurology · 2026Review
- Proteostasis of organelles in aging and disease.The FEBS journal · 2026Review
- Associations between TMEM106B C-terminal fragment aggregation, age, and TDP-43 or tau pathology.Brain pathology (Zurich, Switzerland) · 2026Article
- Expanding Spectrum of FIG4-Related Neurological Disorders of Lysosomal Homeostasis: Case Report and Overview of the Potential Genotype-Phenotype Correlations.Clinical genetics · 2026Review
- Identification of chemicals targeting dementia genes and pathways in the Comparative Toxicogenomics Database.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Genetic frontotemporal degeneration across the lifespan? A critical appraisal of the neurodevelopmental hypothesis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Annexin A11 and TDP-43: core players in neurodegeneration.Acta neuropathologica · 2026Review
- Lysophagy protects against ANXA11 amyloid fibril toxicity and propagation in FTLD.Translational neurodegeneration · 2026Article
- Microglial Dysfunction Induced by C9ORF72 Dipeptide Repeat Proteins: Biomarker and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Biological pathways related to mirna-125a-5p in behavioral variant of frontotemporal dementia.Molecular biology reports · 2026Article
- Aberrant tau accumulation caused by MAPT mutations induces early pathological changes in axonal transport that are rescued by p38α inhibition.Nature neuroscience · 2026Article
- Progranulin deficiency in the brain activates an insulin signaling pathway that may promote neurodegeneration.iScience · 2026Article
- Small heat shock proteins and biomolecular condensates.Cellular and molecular life sciences : CMLS · 2026Review
- Lysosomal homeostasis at the crossroads of neurodegeneration.The Journal of clinical investigation · 2026Review
- A pathogenic Tau mutation drives autophagy-lysosome dysfunction that limits Tau degradation in a model of frontotemporal dementia.Nature communications · 2026Article
- Neurodegeneration risk variants promote lysosomal TMEM106B fibril accumulation.bioRxiv : the preprint server for biology · 2026Article
- Neuro-Dynamic Quantitative Systems Pharmacology (QSP) model describing Alzheimer's disease pathophysiology and treatment effects.NPJ systems biology and applications · 2026Article
- PU.1 restores microglial dysfunction caused by C9ORF72 repeat expansions in neural organoids.Brain : a journal of neurology · 2026Article
- CLN3 mediates chloride efflux from lysosomes.Neuron · 2026Article
- Unraveling Lysosomal Exocytosis: From Molecular Mechanisms to Physiological Functions.Traffic (Copenhagen, Denmark) · 2026Review
93 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are fatal neurodegenerative disorders that are thought to exist on a clinical and pathological spectrum. FTD and ALS are linked by shared genetic causes (e.g. C9orf72 hexanucleotide repeat expansions) and neuropathology, such as inclusions of ubiquitinated, misfolded proteins (e.g. TAR DNA-binding protein 43; TDP-43) in the CNS. Furthermore, some genes that cause FTD or ALS when mutated encode proteins that localize to the lysosome or modulate endosome-lysosome function, including lysosomal fusion, cargo trafficking, lysosomal acidification, autophagy, or TFEB activity. In this review, we summarize evidence that lysosomal dysfunction, caused by genetic mutations (e.g. C9orf72, GRN, MAPT, TMEM106B) or toxic-gain of function (e.g. aggregation of TDP-43 or tau), is an important pathogenic disease mechanism in FTD and ALS. Further studies into the normal function of many of these proteins are required and will help uncover the mechanisms that cause lysosomal dysfunction in FTD and ALS. Mutations or polymorphisms in genes that encode proteins important for endosome-lysosome function also occur in other age-dependent neurodegenerative diseases, including Alzheimer's (e.g. APOE, PSEN1, APP) and Parkinson's (e.g. GBA, LRRK2, ATP13A2) disease. A more complete understanding of the common and unique features of lysosome dysfunction across the spectrum of neurodegeneration will help guide the development of therapies for these devastating diseases.
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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.