Identification of TMED10 as A Regulator for Neuronal Exocytosis of Amyloid Beta 42 by Peixin Meng & Longze Sha & Xiaolin Yu & Yanbing Wang & Erning Zhang & Kexin Meng & Bingnan Li & Qin Zhao & Qi Xu instant download

Identification of TMED10 as A Regulator for Neuronal Exocytosis of Amyloid Beta 42 by Peixin Meng & Longze Sha & Xiaolin Yu & Yanbing Wang & Erning Zhang & Kexin Meng & Bingnan Li & Qin Zhao & Qi Xu instant download

Abstract Alzheimer’s disease (AD) is a neurodegenAβ42 exocytosis and underscore the need for further studies erative disorder characterized by neurotoxic amyloid beta to evaluate its therapeutic potential in AD.(Aβ) deposition in the brain. Neurons can internalize and exocytose Aβ; however, the molecular pathways governing Keywords Alzheimer’s disease · Amyloid beta · Neuron · Aβ release remain poorly understood. To identify key reguExocytosis · TMED10lators of Aβ42 transport, we applied formaldehyde crosslinking of protein complexes combined with co-immunoprecipitation and mass spectrometry analysis to identify IntroductionTMED10 as a novel Aβ42-interacting protein. In cultured neurons, TMED10 knockdown (KD) increased intracelluAlzheimer’s disease (AD) is the most common cause of lar Aβ42 levels by preventing Aβ42 exocytosis. TMED10 dementia, which is characterized by memory loss, as well expression was signifcantly reduced in the cortex of AD as difculties with thinking, language, and problem-solving patients. Overexpression of TMED10 in primary neurons skills [1, 2]. The hallmark histopathological features of AD mitigated the toxic efects of exogenous Aβ42. In 5 × FAD include intracellular neurofbrillary tangles composed of mice, overexpression of TMED10 via tail vein injection of a hyperphosphorylated tau protein and extracellular plaques brain-penetrable adeno-associated virus improved cognitive formed by amyloid-β (Aβ) aggregation [3, 4]. In brain tissue, function and reduced Aβ42 plaque accumulation. Together, Aβ40 is the most abundant amyloid subtype, while Aβ42 is these fndings position TMED10 as a potential regulator of more neurotoxic and pathogenic due to its stronger tendency to aggregate and form an insoluble fbrous amyloid plaque core [5].Peixin Meng and Longze Sha contributed equally to this work.The aggregation of Aβ42 r