ArticleNeuro-degenerative diseases2016
Shared Molecular Mechanisms in Alzheimer's Disease and Amyotrophic Lateral Sclerosis: Neurofilament-Dependent Transport of sAPP, FUS, TDP-43 and SOD1, with Endoplasmic Reticulum-Like Tubules.
Article in Neuro-degenerative diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Proteomic analysis of cerebrospinal fluid of amyotrophic lateral sclerosis patients in the presence of autologous bone marrow derived mesenchymal stem cells.Stem cell research & therapy · 2024Trial
- Unraveling Neurodegenerative Disorders: The Potential of Indole and Imidazole-Based Heterocycles.Current topics in medicinal chemistry · 2026Review
- Linking Cell Architecture to Mitochondrial Signaling in Neurodegeneration: The Role of Intermediate Filaments.International journal of molecular sciences · 2025Review
- Tubular ER dysfunction in neurodegenerative diseases.Neurobiology of disease · 2025Review
- Enhanced secretion of the amyotrophic lateral sclerosis ALS-associated misfolded TDP-43 mediated by the ER-ubiquitin specific peptidase USP19.Cellular and molecular life sciences : CMLS · 2025Article
- Peripherin, A New Promising Biomarker in Neurological Disorders.The European journal of neuroscience · 2025Review
- Differential Expression of Proteins Associated with Bipolar Disorder as Identified Using the PeptideShaker Software.International journal of molecular sciences · 2023Article
- Proteostasis networks in aging: novel insights from text-mining approaches.Biogerontology · 2023Article
- Role of the Intermediate Filament Protein Peripherin in Health and Disease.International journal of molecular sciences · 2022Review
- Review
- Trends in Understanding the Pathological Roles of TDP-43 and FUS Proteins.Advances in experimental medicine and biology · 2021Article
- A Human-Based Functional NMJ System for Personalized ALS Modeling and Drug Testing.Advanced therapeutics · 2020Article
- The Peripherin Gene Regulates the Migration of Bone Marrow Mesenchymal Stem Cells in Wuzhishan Mini Pigs.Stem cells international · 2020Article
- Does SCFD1 rs10139154 Polymorphism Decrease Alzheimer's Disease Risk?Journal of molecular neuroscience : MN · 2019Article
- A PRPH splice-donor variant associates with reduced sural nerve amplitude and risk of peripheral neuropathy.Nature communications · 2019Article
- Formation of Toxic Oligomeric Assemblies of RNA-binding Protein: Musashi in Alzheimer's disease.Acta neuropathologica communications · 2018Article
- TDP-43 and Cytoskeletal Proteins in ALS.Molecular neurobiology · 2018Review
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Authors and funding
2 authors at 1 institution in 1 country.
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Abstract
backgroundAmyotrophic lateral sclerosis (ALS), a debilitating neurodegenerative disorder of the motor neurons, leads to the disorganization of the neurofilament (NF) cytoskeleton and - ultimately - the deterioration of the neuromuscular junction. Some familial cases of ALS are caused by mutated FUS, TDP-43 or SOD1; it is thought that the mutated proteins inflict pathology either by gain or loss of function. The proper function of the neuromuscular junction requires sAPP, a soluble proteolytic fragment of the amyloid-β precursor protein (APP) - a transmembrane protein implicated in the pathology of Alzheimer's disease (AD). Whether sAPP, FUS, TDP-43 and SOD1 are mechanistically linked in a common pathway deregulated in both AD and ALS is not known. SUMMARY: We show that sAPP, TDP-43, FUS and SOD1 are transported to neurite terminals by a mechanism that involves endoplasmic reticulum (ER)-like tubules and requires peripherin NFs. The transport of these proteins, and the translocation of the ER protein reticulon 4 (Rtn4) into neurites was studied in CAD cells, a brainstem-derived neuronal cell line highly relevant to AD and ALS. We show that a significant fraction of sAPP is generated in the soma and accumulates in a juxtanuclear ER subdomain. In neurites, sAPP localizes to Rtn4-positive ER-like tubules that extend from the soma into the growth cone and colocalizes with peripherin NFs. Knocking down peripherin disrupts the NF network and diminishes the accumulation of sAPP, TDP-43, FUS, SOD1 and Rtn4 at terminals. KEY MESSAGES: We propose that the impediment of a common, ER-mediated mechanism of transport of sAPP, TDP-43, FUS and SOD1, caused by a disrupted NF network, could be part of the mechanisms leading to AD and ALS.
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