title: Dysregulatory dysequilibrium of gene transcription and of nuclear transport in polyglutamine neuro-degeneration.
abstract: Polyglutamine neurodegeneration as an essential expansion mutation of the CAG-trinucleotide repeat encoding glutamine would appear to constitute an integral process of aggregation/accumulation that self-propagates a secondary process of possible nuclear sequestration. Within such a scheme of progressive expansion of polyglutamine stretches in strict parallel correlation with increased CAG trinucleotide repeats in genes such as ataxin-7 and its messenger RNA, it would appear that a fundamental relationship of accumulation directly inducing biophysical disruption between nuclear/nucleolar and cytoplasmic protein machineries would constitute a dysfunctional dysequilibrium accounting for self-progressive neuronal degeneration with atrophy of the cerebral cortex and ganglia such as the caudate, that is limited often to specific population groups of neurons. It is for example in terms of Huntington's disease as an autosomal dominant disorder with high penetrance on a background of onset of dementia mainly in the fourth and fifth decades of life that one might conceive of polyglutamine neurodegeneration as fundamentally a developmental disturbance affecting neuronal maturation that accounts for abnormal neurophysiological and biochemical aspects of interaction of nucleus with cytoplasm. Polyglutamine expansion and trinucleotide repeats as both progressive processes of accumulation and synthesis would constitute a complex interplay of inducing and induced effects that both contribute in probably multiple ways to the self-progressive nature of a nuclear sequestration process.
authors.affiliation: Department of Pathology, St. Luke's Hospital, University of Malta, Malta. lawrence.agius@um.edu.mt
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Agius
mesh_terms: D021581:Active Transport, Cell Nucleus; D000222:Adaptation, Physiological; D000067719:Ataxin-7; D002467:Cell Nucleus / Q000378:metabolism*; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D009410:Nerve Degeneration / Q000235:genetics* / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000235:genetics* / Q000378:metabolism*; D020754:Spinocerebellar Ataxias / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C000593829:ATXN7 protein, human; D000067719:Ataxin-7; D009419:Nerve Tissue Proteins; D010455:Peptides; C097188:polyglutamine