![]() ![]() Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer’s disease. Giannakopoulos P, Herrmann FR, Bussiere T, Bouras C, Kovari E, Perl DP, et al. Prevalence of Alzheimer’s disease in very elderly people: a prospective neuropathological study. Polvikoski T, Sulkava R, Myllykangas L, Notkola IL, Niinisto L, Verkkoniemi A, et al. Alzheimer’s Amyloid-β is an antimicrobial peptide: a review of the evidence. Given AD’s association with infection and that overloading AMP may exacerbate AD, this study suggests that LL-37, which is up-regulated upon infection, may be a driving force behind AD by acting as an endogenous agonist of CLIC1. In mouse and monkey models, LL-37 caused significant pathological phenotypes linked to AD, including elevated amyloid-β, increased neurofibrillary tangles, enhanced neuronal death and brain atrophy, enlargement of lateral ventricles, and impairment of synaptic plasticity and cognition, while Clic1 knockout and blockade of LL-37-CLIC1 interactions inhibited these phenotypes. It also activates CLIC1 to cause microglial hyperactivation, neuroinflammation, and excitotoxicity. ![]() ![]() Here, we found that the human antimicrobial peptide (AMP) LL-37 promoted CLIC1 membrane translocation and integration. However, the formation and activation mechanisms of functional CLIC1 are unknown. As a prime mover in Alzheimer’s disease (AD), microglial activation requires membrane translocation, integration, and activation of the metamorphic protein chloride intracellular channel 1 (CLIC1), which is primarily cytoplasmic under physiological conditions. ![]()
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