Cellular and molecular mechanisms involved in the selective vulnerability of striatal projection neurons in Huntington's disease.
Neurodegenerative disorders affecting the central nervous system, such as Alzheimer's disease, Parkinson's disease, Huntington's chorea (HD) and amyotrophic lateral sclerosis are characterized by the loss of selected neuronal populations. Another striking feature shared by these diseases is the deposition of proteinaceous inclusion bodies in the brain, which may be intracytoplasmatic or intranuclear, or even extracellular. However, the density and prevalence of aggregates are not always directly related to neurodegeneration. Although some of these diseases are the result of mutations in known proteins, with HD a clear example, the expression and location of the affected protein do not explain the selective neurodegeneration. Therefore, other intrinsic mechanisms, characteristic of each neuronal population, might be involved in the neurodegenerative process. In this review we focus on several proposed mechanisms such as excitotoxicity, mitochondrial dysfunction and altered expression of trophic factors, which could account for the pathogenesis of HD.
Pérez-Navarro
E
E
Department of Cell Biology and Pathology, Faculty of Medicine, IDIBAPS, University of Barcelona, Barcelona, Spain.
Canals
J M
JM
Ginés
S
S
Alberch
J
J
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000473:pathology*; D007395:Interneurons / Q000473:pathology*; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D009154:Mutation; D009410:Nerve Degeneration / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins