Therapies for Tau-associated neurodegenerative disorders:targeting molecules,synapses,and cells

Miranda Robbins

摘要：Advances in experimental and computational technologies continue to grow rapidly to provide novel avenues for the treatment of neurodegenerative disorders.Despite this,there remain only a handful of drugs that have shown success in late-stage clinical trials for Tau-associated neurodegenerative disorders.The most commonly prescribed treatments are symptomatic treatments such as cholinesterase inhibitors and N-methyl-D-aspartate receptor blockers that were approved for use in Alzheimer's disease.As diagnostic screening can detect disorders at earlier time points,the field needs pre-symptomatic treatments that can prevent,or significantly delay the progression of these disorders(Koychev et al.,2019).These approaches may be different from late-stage treatments that may help to ameliorate symptoms and slow progression once symptoms have become more advanced should early diagnostic screening fail.This mini-review will highlight five key avenues of academic and industrial research for identifying therapeutic strategies to treat Tau-associated neurodegenerative disorders.These avenues include investigating(1)the broad class of chemicals termed"small molecules";(2)adaptive immunity through both passive and active antibody treatments;(3)innate immunity with an emphasis on microglial modulation;(4)synaptic compartments with the view that Tau-associated neurodegenerative disorders are synaptopathies.Although this mini-review will focus on Alzheimer's disease due to its prevalence,it will also argue the need to target other tauopathies,as through understanding Alzheimer's disease as a Tau-associated neurodegenerative disorder,we may be able to generalize treatment options.For this reason,added detail linking back specifically to Tau protein as a direct therapeutic target will be added to each topic.