Neurodegenerative disorders,metabolic icebergs,and mitohormesis  

作　　者：Matthew C.L.Phillips Martin Picard 

机构地区：[1]Department of Neurology,Waikato Hospital,Hamilton 3204,New Zealand [2]Department of Medicine,University of Auckland,Auckland 1142,New Zealand [3]Division of Behavioral Medicine,Department of Psychiatry,Columbia University Irving Medical Center,New York,NY 10032,USA [4]Department of Neurology,H.Houston Merritt Center,Columbia Translational Neuroscience Initiative,Columbia University Irving Medical Center,New York,NY 10032,USA [5]New York State Psychiatric Institute,New York,NY 10032,USA [6]Robert N Butler Columbia Aging Center,Columbia University Mailman School of Public Health,New York,NY,USA

出　　处：《Translational Neurodegeneration》2024年第1期388-408,共21页转化神经变性病(英文)

摘　　要：Neurodegenerative disorders are typically“split”based on their hallmark clinical,anatomical,and pathological features,but they can also be“lumped”by a shared feature of impaired mitochondrial biology.This leads us to present a scientific framework that conceptualizes Alzheimer’s disease(AD),Parkinson’s disease(PD),amyotrophic lateral sclerosis(ALS),and Huntington’s disease(HD)as“metabolic icebergs”comprised of a tip,a bulk,and a base.The visible tip conveys the hallmark neurological symptoms,neurodegenerative regions,and neuronal protein aggregates for each disorder.The hidden bulk depicts impaired mitochondrial biology throughout the body,which is multifaceted and may be subdivided into impaired cellular metabolism,cell-specific mitotypes,and mitochondrial behaviours,functions,activities,and features.The underlying base encompasses environmental factors,especially modern industrial toxins,dietary lifestyles,and cognitive,physical,and psychosocial behaviours,but also accommodates genetic factors specific to familial forms of AD,PD,and ALS,as well as HD.Over years or decades,chronic exposure to a particular suite of environmental and genetic factors at the base elicits a trajectory of impaired mitochondrial biology that maximally impacts particular subsets of mitotypes in the bulk,which eventually surfaces as the hallmark features of a particular neurodegenerative disorder at the tip.We propose that impaired mitochondrial biology can be repaired and recalibrated by activating“mitohormesis”,which is optimally achieved using strategies that facilitate a balanced oscillation between mitochondrial stressor and recovery phases.Sustainably harnessing mitohormesis may constitute a potent preventative and therapeutic measure for people at risk of,or suffering with,neurodegenerative disorders.

关 键 词：Alzheimer’s disease Parkinson’s disease Amyotrophic lateral sclerosis Huntington’s disease Splitting LUMPING MITOCHONDRIA Mitotypes HORMESIS Mitohormesis 

分 类 号：R741[医药卫生—神经病学与精神病学]