Molecular Mechanisms and Potential Therapeutical Targets in Huntington's Disease

Chiara Zuccato, Marta Valenza, Elena Cattaneo
2010 Physiological Reviews  
I. Introduction II. General Introduction to Huntington's Disease A. Historical background B. Neuropathology C. Symptoms D. Gene hunters E. Genetic modifiers of HD F. Modeling HD III. The Normal Function of Huntingtin A. Huntingtin through evolution B. Structure C. Cellular and tissue distribution D. Huntingtin interactors E. Huntingtin functions F. Loss of wild-type huntingtin function in HD IV. Mechanisms of Neurodegeneration A. Loss of BDNF B. Excitoxicity and corticostriatal dysfunction C.
more » ... oteolysis D. Misfolding, aggregation, and clearance of mutant huntingtin E. Autophagy F. Mitochondrial dysfunctions G. Transcriptional dysregulation H. Summary and conclusions V. Therapeutic Strategies Against Pathogenic Mechanisms A. Drugs against excitotoxicity B. Strategies to increase BDNF in HD C. Targeting caspase activities and huntingtin proteolysis D. Targeting aggregation E. Drugs against mitochondrial dysfunction F. Targeting gene transcription G. Summary and conclusions VI. Targeting Mutant Huntingtin A. Targeting mutant huntingtin RNA: antisense oligonucleotide and RNA interference B. Targeting the mutant protein: artificial peptides and intrabodies VII. Targeting Cell Loss: Cell Replacement Approaches VIII. Biomarkers in Huntington's Disease A. Imaging studies B. Metabolomic, proteomic, and transcriptomic approaches C. Biomarkers built on Hypothesis-Driven experiments IX. Conclusions
doi:10.1152/physrev.00041.2009 pmid:20664076 fatcat:x34xcxbgvrcyxgzjohy67b5zoy