How do neurons age?A focused review on the aging of the microtubular cytoskeleton  

作　　者：Brad Richardson Thomas Goedert Shmma Quraishe Katrin Deinhardt Amritpal Mudher 

机构地区：[1]School of Biological Sciences,University of Southampton,Southampton,UK [2]Institute of Developmental and Regenerative Medicine,University of Oxford,Oxford,UK

出　　处：《Neural Regeneration Research》2024年第9期1899-1907,共9页中国神经再生研究（英文版）

基　　金：funded by the Gerald Kerkut Charitable Trust (GKT)(to BR)

摘　　要：Aging is the leading risk factor for Alzheimer’s disease and other neurodegenerative diseases. We now understand that a breakdown in the neuronal cytoskeleton, mainly underpinned by protein modifications leading to the destabilization of microtubules, is central to the pathogenesis of Alzheimer’s disease. This is accompanied by morphological defects across the somatodendritic compartment, axon, and synapse. However, knowledge of what occurs to the microtubule cytoskeleton and morphology of the neuron during physiological aging is comparatively poor. Several recent studies have suggested that there is an age-related increase in the phosphorylation of the key microtubule stabilizing protein tau, a modification, which is known to destabilize the cytoskeleton in Alzheimer’s disease. This indicates that the cytoskeleton and potentially other neuronal structures reliant on the cytoskeleton become functionally compromised during normal physiological aging. The current literature shows age-related reductions in synaptic spine density and shifts in synaptic spine conformation which might explain age-related synaptic functional deficits. However, knowledge of what occurs to the microtubular and actin cytoskeleton, with increasing age is extremely limited. When considering the somatodendritic compartment, a regression in dendrites and loss of dendritic length and volume is reported whilst a reduction in soma volume/size is often seen. However, research into cytoskeletal change is limited to a handful of studies demonstrating reductions in and mislocalizations of microtubule-associated proteins with just one study directly exploring the integrity of the microtubules. In the axon, an increase in axonal diameter and age-related appearance of swellings is reported but like the dendrites, just one study investigates the microtubules directly with others reporting loss or mislocalization of microtubule-associated proteins. Though these are the general trends reported, there are clear disparities between model organisms and

关 键 词：age-related changes AGING CYTOSKELETON MICROTUBULES neuronal morphology 

分 类 号：R338[医药卫生—人体生理学]