Henderson Robert David, Kepp Kasper Planeta, Eisen Andrew
Department of Neurology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
Department of Chemistry, Technical University of Denmark, Kongens Lyngby, Denmark.
Front Neurol. 2022 May 27;13:890203. doi: 10.3389/fneur.2022.890203. eCollection 2022.
Amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) are neurodegenerations with evolutionary underpinnings, expansive clinical presentations, and multiple genetic risk factors involving a complex network of pathways. This perspective considers the complex cellular pathology of aging motoneuronal and frontal/prefrontal cortical networks in the context of evolutionary, clinical, and biochemical features of the disease. We emphasize the importance of evolution in the development of the higher cortical function, within the influence of increasing lifespan. Particularly, the role of aging on the metabolic competence of delicately optimized neurons, age-related increased proteostatic costs, and specific genetic risk factors that gradually reduce the energy available for neuronal function leading to neuronal failure and disease.
肌萎缩侧索硬化症和额颞叶痴呆（ALS/FTD）是具有进化基础、临床表现多样且涉及复杂通路网络的多种遗传风险因素的神经退行性疾病。本文从该疾病的进化、临床和生化特征的角度，探讨了衰老的运动神经元和额叶/前额叶皮质网络的复杂细胞病理学。我们强调在寿命延长的影响下，进化在高级皮质功能发展中的重要性。特别是衰老对精细优化的神经元代谢能力的作用、与年龄相关的蛋白质稳态成本增加，以及特定的遗传风险因素，这些因素会逐渐减少神经元功能可用的能量，导致神经元功能衰竭和疾病。
