[Molecular basis of Huntington's disease and possible pathogenic mechanisms].
BACKGROUND
Huntington s disease is one of the, at least, nine neurological disorders caused by a CAG triplet expansion coding for a poly glutamine sequence in the corresponding protein. Huntington s disease affects 3 7 in 100.000 individuals in Western Europe descendent population and the symptomatology comprises motor (including chorea and rigidity), cognitive (subcortical dementia), and psychological (including irritability and depression) manifestations until death.


METHODS
Neuropathology is extremely restricted, with atrophy occurring in the striatum and, to a lesser extent, in the cerebral cortex. Microscopically, the neuropathology is characterized by neuronal loss, reactive gliosis, and intraneuronal protein aggregates. Since the initial description of this disease by George Huntington in 1872, substantial advance has been achieved in the understanding of this pathology. The pathogenic gene and mutation were identified in 1993. This allowed the generation of multiple in vitro, cellular, and animal models of Huntington s disease. These studies have originated multiple hypotheses regarding the mechanism by which huntingtin with an expanded poly glutamine tract exerts its toxicity.


CONCLUSIONS
We try to summarize the current knowledge about this disease from the clinical manifestations to the molecular basis, in an attempt to offer a global view of this pathology.
Martín Aparicio
E
E
Centro de Biologia Molecular Severo Ochoa. Consejo Superior de Investigaciones Científicas (CSIC)/UAM, Madrid, España.
Lucas
J J
JJ
D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology; D010455:Peptides / Q000502:physiology
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; C097188:polyglutamine