ArticleThe Journal of biological chemistry2009
Dynein dysfunction induces endocytic pathology accompanied by an increase in Rab GTPases: a potential mechanism underlying age-dependent endocytic dysfunction.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 41 citations in OpenAlex.
- Transcriptional Landscape and Biomarker Discovery for Endoplasmic Reticulum Stress in Alzheimer's Disease: An Ex Vivo Study Using Patients-Derived Dermal Fibroblasts.Psychiatry investigation · 2025Article
- Apolipoprotein E2 Expression Alters Endosomal Pathways in a Mouse Model With Increased Brain Exosome Levels During Aging.Traffic (Copenhagen, Denmark) · 2024Article
- Beware of Misdelivery: Multifaceted Role of Retromer Transport in Neurodegenerative Diseases.Frontiers in aging neuroscience · 2022Review
- Polyphosphate expression by cancer cell extracellular vesicles mediates binding of factor XII and contact activation.Blood advances · 2021Article
- Extracellular Vesicles and Immune System in Ageing and Immune Diseases.Experimental neurobiology · 2021Review
- Exosomal Proteins and miRNAs as Mediators of Amyotrophic Lateral Sclerosis.Frontiers in cell and developmental biology · 2021Review
- TMEM30A is a candidate interacting partner for the β-carboxyl-terminal fragment of amyloid-β precursor protein in endosomes.PloS one · 2018Article
- Dynein disruption perturbs post-synaptic components and contributes to impaired MuSK clustering at the NMJ: implication in ALS.Scientific reports · 2016Article
- Diabetes Mellitus Induces Alzheimer's Disease Pathology: Histopathological Evidence from Animal Models.International journal of molecular sciences · 2016Review
- Exosomes as a Nanodelivery System: a Key to the Future of Neuromedicine?Molecular neurobiology · 2016Review
- Aging, Alzheimer's, and APOE genotype influence the expression and neuronal distribution patterns of microtubule motor protein dynactin-P50.Frontiers in cellular neuroscience · 2015Article
- Diabetes mellitus accelerates Aβ pathology in brain accompanied by enhanced GAβ generation in nonhuman primates.PloS one · 2015Article
- Hook proteins: association with Alzheimer pathology and regulatory role of hook3 in amyloid beta generation.PloS one · 2015Article
- C9ORF72, implicated in amytrophic lateral sclerosis and frontotemporal dementia, regulates endosomal trafficking.Human molecular genetics · 2014Article
- Alteration of dynein function affects α-synuclein degradation via the autophagosome-lysosome pathway.International journal of molecular sciences · 2013Article
- G proteins, p60TRP, and neurodegenerative diseases.Molecular neurobiology · 2013Review
- Mitochondrial base excision repair in mouse synaptosomes during normal aging and in a model of Alzheimer's disease.Neurobiology of aging · 2012Article
- Rab GTPases, membrane trafficking and diseases.Current drug targets · 2011Review
Corrections and comments
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Authors and funding
5 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Growing evidence suggests that endocytic dysfunction is intimately involved in early stage Alzheimer disease pathology, such as the accumulation of beta-amyloid precursor protein in enlarged early endosomes. However, it remains unclear how endocytic dysfunction is induced in an age-dependent manner. Cytoplasmic dynein, a microtubule-based motor protein, interacts with another microtubule-associated protein, dynactin. The resulting dynein-dynactin complex mediates minus end-directed vesicle transport, including endosome trafficking. We have previously shown that the interaction between dynein-dynactin complexes is clearly attenuated in aged monkey brains, suggesting that dynein-mediated transport dysfunction exists in aged brains. Our immunohistochemical analyses revealed that age-dependent endocytic pathology was accompanied by an increase in Rab GTPases in aged monkey brains. Here, we demonstrated that siRNA-induced dynein dysfunction reproduced the endocytic pathology accompanied by increased Rab GTPases seen in aged monkey brains and significantly disrupted exosome release. Moreover, it also resulted in endosomal beta-amyloid precursor protein accumulation characterized by increased beta-site cleavage. These findings suggest that dynein dysfunction may underlie age-dependent endocytic dysfunction via the up-regulation of Rab GTPases. In addition, this vicious circle may worsen endocytic dysfunction, ultimately leading to Alzheimer disease pathology.
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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.