Please use this identifier to cite or link to this item: https://hdl.handle.net/10216/105022
Author(s): Ana Leitao Rocha
Pedro Guedes Dias
Brigida R Pinho
Jorge M A Oliveira
Title: Trends in Mitochondrial Therapeutics for Neurological Disease
Issue Date: 2015
Abstract: Neuronal homeostasis is critically dependent on healthy mitochondria. Mutations in mitochondrial DNA (mtDNA), in nuclear-encoded mitochondrial components, and age-dependent mitochondrial damage, have all been connected with neurological disorders. These in clude not only typical mitochondrial syndromes with neurological features such as encephalomyopathy, myoclonic epilepsy, neuropathy and ataxia; but also secondary mitochondrial involvement in neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's disease. Unravelling the molecular aetiology of mitochondrial dysfunction opens new therapeutic prospects for diseases thus far lacking effective treatments. In this review we address recent advances on preventive strategies, such as pronuclear, spindle-chromosome complex, or polar body genome transfer to replace mtDNA and avoid disease transmission to newborns; we also address experimental mitochondrial therapeutics aiming to benefit symptomatic patients and prevent disease manifestation in those at risk. Specifically, we focus on: (1) gene therapy to reduce mutant mtDNA, such as anti-replicative therapies and mitochondria-targeted nucleases allowing favourable heteroplasmic shifts; (2) allotopic expression of recoded wild-type mitochondrial genes, including targeted tRNAs and xenotopic expression of cognate genes to compensate for pathogenic mutations; (3) mitochondria targeted-peptides and lipophilic cations for in vivo delivery of antioxidants or other putative therapeutics; and (4) modulation of mitochondrial dynamics at the level of biogenesis, fission, fusion, movement and mitophagy. Further advances in therapeutic development are hindered by scarce in vivo models for mitochondrial disease, with the bulk of available data coming from cellular models. Nevertheless, wherever available, we also address data from in vivo experiments and clinical trials, focusing on neurological disease models.
Subject: Medicina básica
Basic medicine
Scientific areas: Ciências médicas e da saúde::Medicina básica
Medical and Health sciences::Basic medicine
URI: https://repositorio-aberto.up.pt/handle/10216/105022
Related Information: info:eu-repo/grantAgreement/FCT - Fundação para a Ciência e Tecnologia/Operacional Factores de Competitividade/PTDC/NEU-NMC/0237/2012/Inibição de KDACs e dinâmica intracelular: impacto no desenvolvimento, sobrevivência e transmissão NEUROnal /KDAC´S
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
Appears in Collections:FFUP - Artigo em Revista Científica Internacional

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