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Progress in NeurobiologyVolume 141, 1 June 2016, Pages 61-82

The cytoskeleton as a novel therapeutic target for old neurodegenerative disorders(Review)

  • aNeurodegeneration Group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, 4200, Portugal
  • bInstituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, 4200, Portugal
  • cNerve Regeneration Group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, 4200, Portugal

Abstract

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. © 2016 Elsevier Ltd.

Author keywords

Glycogen synthase kinase 3 β inhibitorsHistone deacetylase inhibitorsMicrotubule stabilizersNeurodegenerative disordersNeuronal cytoskeletonROCK inhibitors

Indexed keywords

EMTREE drug terms:1 (4 methoxybenzyl) 3 (5 nitro 2 thiazolyl)urea4 (1 aminoethyl) n (4 pyridyl)cyclohexanecarboxamideactin binding proteinantineoplastic agentcollapsin response mediator protein 2epothilone Dfasudilhistone deacetylasephosphotransferaseresveratrolricolinostattideglusibtubulinvalproic acid
EMTREE medical terms:actin filamentAlzheimer diseaseamyotrophic lateral sclerosisautophagycell functioncell polaritycytoskeletondegenerative diseasedrug targetingenzyme inhibitionhereditary motor sensory neuropathyhumanHuntington choreamicrotubulenerve cellnerve cell lesionnerve fiber transportneurologic diseaseneuropathologynonhumanParkinson diseasephase 1 clinical trial (topic)phase 2 clinical trial (topic)phase 3 clinical trial (topic)priority journalReviewagingcytoskeletondrug effectsmetabolismNeurodegenerative Diseasesphysiology
MeSH:AgingCytoskeletonHumansNeurodegenerative Diseases

Chemicals and CAS Registry Numbers:

1 (4 methoxybenzyl) 3 (5 nitro 2 thiazolyl)urea, 487021-52-3; 4 (1 aminoethyl) n (4 pyridyl)cyclohexanecarboxamide, 146986-50-7; fasudil, 103745-39-7; histone deacetylase, 9076-57-7; phosphotransferase, 9031-09-8, 9031-44-1; resveratrol, 501-36-0; ricolinostat, 1316214-52-4; tideglusib, 865854-05-3; valproic acid, 1069-66-5, 99-66-1

Drug tradename:

  • acy 1215,
  • ar a 014418,
  • y 27632

Funding details

Funding sponsor Funding number Acronym
Programa Operacional Temático Factores de Competitividade
Fundação para a Ciência e a Tecnologia
See opportunities		FCOMP-01-0124-FEDER-017455,HMSP-ICT/0020/2010,FCOMP-01-0124-FEDER-021392,PTDC/SAU-ORG/118863/2010,NORTE-07-0124-FEDER-000001-Neurodegenerative
Fundação para a Ciência e a Tecnologia
See opportunities

  • 1

    We apologize to those investigators whose work we could not cite due to the space limitations, and gratefully acknowledge their contributions to this field. We acknowledge Marina Silva for assistance with bibliography organization. The authors were supported by FEDER through the Operational Competitiveness Programme – COMPETE and by National Funds through FCT – Fundação para a Ciência e a Tecnologia under the projects FCOMP-01-0124-FEDER-017455 ( HMSP-ICT/0020/2010 ) (M.M.S.) and FCOMP-01-0124-FEDER-021392 ( PTDC/SAU-ORG/118863/2010 ) (J.E. and M.A.L.). M.A.L. was also supported by the project NORTE-07-0124-FEDER-000001-Neurodegenerative disorders (co- funded by QREN , FEDER and FCT ).

  • ISSN: 03010082
  • CODEN: PGNBA
  • Source Type: Journal
  • Original language: English
  • DOI: 10.1016/j.pneurobio.2016.04.007
  • PubMed ID: 27095262
  • Document Type: Review
  • Publisher: Elsevier Ltd

  Liz, M.A.; Neurodegeneration Group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal;
© Copyright 2017 Elsevier B.V., All rights reserved.

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