The cytoskeleton as a novel therapeutic target for old neurodegenerative disorders.
Cytoskeleton defects, including alterations in microtubule stability, in axonal transport as well as in actin dynamics, have been characterized in several unrelated neurodegenerative conditions. These observations suggest that defects of cytoskeleton organization may be a common feature contributing to neurodegeneration. In line with this hypothesis, drugs targeting the cytoskeleton are currently being tested in animal models and in human clinical trials, showing promising effects. Drugs that modulate microtubule stability, inhibitors of posttranslational modifications of cytoskeletal components, specifically compounds affecting the levels of tubulin acetylation, and compounds targeting signaling molecules which regulate cytoskeleton dynamics, constitute the mostly addressed therapeutic interventions aiming at preventing cytoskeleton damage in neurodegenerative disorders. In this review, we will discuss in a critical perspective the current knowledge on cytoskeleton damage pathways as well as therapeutic strategies designed to revert cytoskeleton-related defects mainly focusing on the following neurodegenerative disorders: Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Amyotrophic Lateral Sclerosis and Charcot-Marie-Tooth Disease.
Neurodegeneration Group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200 Porto, Portugal; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200 Porto, Portugal.
Jessica
J
Eira
Neurodegeneration Group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200 Porto, Portugal; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200 Porto, Portugal.
Catarina Santos
CS
Silva
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200 Porto, Portugal; Nerve Regeneration Group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200 Porto, Portugal.
Mónica Mendes
MM
Sousa
Neurodegeneration Group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200 Porto, Portugal; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200 Porto, Portugal. Electronic address: maliz@ibmc.up.pt.
Márcia Almeida
MA
Liz
D000375:Aging; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000628:therapy*
Glycogen synthase kinase 3 β inhibitors; Histone deacetylase inhibitors; Microtubule stabilizers; Neurodegenerative disorders; Neuronal cytoskeleton; ROCK inhibitors