Ask about this productRelated genes to: Rab10 Blocking Peptide
- Gene:
- RAB10 NIH gene
- Name:
- RAB10, member RAS oncogene family
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 2p23.3
- Locus Type:
- gene with protein product
- Date approved:
- 1999-07-30
- Date modifiied:
- 2014-11-18
Related products to: Rab10 Blocking Peptide
Related articles to: Rab10 Blocking Peptide
- Mutations in the gene are the most frequent cause of familial Parkinson's disease (PD) whereas common variants are associated with an increased risk for sporadic PD. encodes a multi-domain protein displaying two functional enzymatic activities: GTPase and kinase. Familial mutations have been linked to alterations in its GTPase and kinase activities, elevated substrate phosphorylation, as well as increased neurotoxicity in cell and animal models. In addition to familial mutations, several common coding variants have been associated with PD risk in different ethnic populations. Little is known about how these coding variants modulate the risk of developing PD. In this study, we aim to evaluate whether a collection of coding risk variants (A419V, N551K, R1398H, R1628P, M1646T, S1647T, G2385R) modify the biochemical properties of the LRRK2 protein and LRRK2-mediated neurotoxicity using cell-based assays. With the exception of G2385R, we find that coding risk variants have minimal impact on LRRK2 steady-state protein levels, GTP-binding, phosphorylation at Ser910, Ser935, and Ser1292, and subcellular localization in human cell lines and cultured primary neurons. G2385R reduces the steady-state levels of LRRK2 and exhibits reduced phosphorylation at Ser910/Ser935 and Ser1292, consistent with diminished kinase activity. Notably, however, variants associated with increased PD risk (A419V, R1628P, M1646T, and G2385R) significantly elevate the levels of LRRK2-mediated Rab10 phosphorylation by two-fold in cells. In contrast, variants associated with reduced PD risk (N551K, R1398H, and N551K-R1398H) do not alter normal LRRK2-mediated pRab10 levels. Intriguingly, we find that both PD-risk and PD-protective LRRK2 variants can respond normally to kinase activation by different lysosomal stressors (chloroquine, nigericin and monensin) to robustly induce pRab10 levels in cells. The PD risk variant, G2385R LRRK2, significantly inhibits neurite outgrowth in primary cortical neurons compared to wild-type LRRK2. Combining each coding risk variant with the familial G2019S mutation has minimal impact on the elevated kinase activity of G2019S LRRK2 or its capacity to inhibit neurite outgrowth. Our study indicates that LRRK2-dependent Rab phosphorylation represents a relevant readout of PD risk induced by coding variants and demonstrates that the PD risk variant, G2385R LRRK2, creates a hyperactive kinase that can impair neuronal integrity at comparable levels to the effects of G2019S LRRK2. - Source: PubMed
Publication date: 2026/04/27
Nguyen An Phu TranMoser RogerBryant NicoleCunningham Lindsey AWorden Evan JMoore Darren J - The diagnosis of neonatal respiratory distress syndrome NRDS relies on progressive breathing difficulties after birth, abnormal blood oxygen levels, and typical chest X-ray images. However, this diagnostic method has insufficient specificity and is difficult to make a differential diagnosis. Pulmonary surfactant replacement and respiratory support are the main treatment methods for NRDS, but targeted therapy is still lacking. Serum miRNA detection has high sensitivity and specificity. This study explored the miR-574-5p/RAB10 axis, providing potential molecular targets for the early diagnosis and treatment development of NRDS. - Source: PubMed
Publication date: 2026/04/19
Ji YananZhou YangpingDeng LudanHu Ting - Flaviviruses intricately rewire host metabolic networks to establish a replication-permissive environment; however, the role of glucose transporter-mediated uptake, particularly via glucose transporter 4 (GLUT4), remains insufficiently defined. Japanese encephalitis virus (JEV) infection induces extensive remodeling of glucose metabolism, exemplified by the coordinated upregulation of critical metabolic effectors. Pharmacological blockade of glucose metabolic pathways markedly attenuates JEV replication, whereas exogenous glucose supplementation enhances viral propagation in a concentration-dependent manner. A targeted screen of 111 metabolism-oriented compounds identified selective GLUT4 inhibitors with potent antiviral efficacy. Notably, GLUT4 expression is consistently upregulated during JEV infection across multiple cell types, albeit to varying degrees, and is similarly induced by duck Tembusu virus (DTMUV), suggesting a potentially conserved mechanism shared by these two flaviviruses. However, broader validation across additional members of the Flavivirus genus remains warranted. Mechanistically, the viral nonstructural protein 3 (NS3) engages insulin receptor substrate 1 (IRS1), thereby activating the IRS1-PI3K-Akt-mTORC1-SREBP-1c signaling axis to transcriptionally drive GLUT4 expression. Concurrently, JEV infection induces PI3K-Akt-dependent phosphorylation of AS160, promoting GLUT4 vesicular trafficking via the coordinated action of Rab8 and Rab10. Collectively, these findings delineate a previously unrecognized mechanism whereby JEV commandeers host insulin signaling to orchestrate GLUT4 biosynthesis and membrane translocation, thereby ensuring continuous metabolic substrate availability to sustain replication. This GLUT4-centric metabolic circuitry represents a mechanistically tractable target for host-directed antiviral strategies against Flavivirus. - Source: PubMed
Publication date: 2026/04/17
Wang QiHao PingZhu Sheng-YanZhou Jiang-FeiFeng ShengDai QiWei Jian-ChaoGo Yun YoungChen JingZhou Bin - Common and rare genetic variants in leucine-rich repeat kinase 2 (LRRK2) have been linked with sporadic and familial Parkinson's disease (PD). Recently, we discovered that common genetic variation near the LRRK2 locus determined survival in progressive supranuclear palsy (PSP). Our study aimed to explore biomarkers of LRRK2 and lysosomal dysfunction in PSP. - Source: PubMed
Publication date: 2026/04/15
Nielsen Louise-KristineFrost Joshua L IVaughan David PReal RaquelFumi RionaJensen Marte TheilmannHodgson MeganStafford Eleanor JWu LesleyAnsorge OlafQuaegebeur AnneliesAllinson Kieren S JWarner Thomas TJaunmuktane ZaneMisbahuddin AnjumLeigh P NigelGhosh Boyd C PBhatia Kailash PChurch AlistairKobylecki ChristopherHu Michele T MRowe James BShomo Alan AGraham Danielle LMabrouk Omar SMorris Huw RSammler Esther MJabbari Edwin - : Alzheimer's disease (AD) is defined by amyloid-β plaques and tau neurofibrillary tangles and is typically associated with progressive cognitive decline. However, a substantial subset of individuals remains cognitively intact despite intermediate-to-high AD pathology, a phenomenon termed cognitive resilience. This review aims to synthesize genetic variants and biological pathways associated with preserved cognition in the presence of AD neuropathology. : We performed a narrative thematic synthesis of human genetic studies (GWAS, sequencing, biomarker-informed cohorts) and extreme resilience case reports. Variants were prioritized by replication, mechanistic plausibility, and relevance to clinicopathologic dissociation, and were organized by shared biological pathways. When applicable, cognitive resilience was operationalized using residual-based approaches modeling cognitive performance after adjustment for neuropathological burden, age, sex, and education or cognitive reserve proxies reported by each cohort. : Recurrent resilience-associated variants include ε2, -Christchurch, -COLBOS, , , , , , , and synapse-linked markers such as . These variants converge on lipid metabolism, synaptic function and neuroplasticity, tau regulation and proteostasis, immune and inflammatory signaling, vascular/BBB resilience, and RNA regulation. : Genetic determinants of cognitive resilience highlight mechanisms that preserve neural integrity independent of pathological load. Targeting resilience pathways may enable precision therapies designed to maintain cognitive function in AD. - Source: PubMed
Publication date: 2026/03/03
Burdman GabrielAkkaoui JulietColon NataliaPerez AndresLakshmana Madepalli K