Heat Shock Proteins In Poly Glutamine Model
Expansion of CAG trinucleotide repeats encoding poly glutamine (poly Q) tract in other wise unrelated proteins are responsible to atleast nine diseases . These diseases include Huntington’s disease (HD), spinobulbar muscular atrophy, dentatorubral pallidoluysian atrophy, and spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7, and 17.(1) Clinical features include ataxia and other movement disorders, loss of cognitive ability, and psychiatric disabilities(2). A characteristic feature of polyQ diseases is the formation of insoluble, granular, and fibrous deposits in affected neurons termed neuronal inclusions, which have …show more content…
The disease is caused by the expansion of a polyQ segment located within the first exon of the gene encoding huntingtin, an 350-kDa protein. The neuronal inclusions in HD have fibrillar morphology and contain aggregated amino-terminal fragments of huntingtin . Similar inclusions containing aggregated polyQ proteins were reported in other polyQ diseases.(1,2)Previous studies have shown that two process namely the autophagy and the proteasomal system were mainly involved in the removal of these aggregates (3,5). From cellular studies, it has become clear that certain heat shock proteins, as molecular chaperones, form a potent natural defense against proteotoxic stress induced by these protein misfolding diseases(3,5). Heat-shock proteins are divided into several main families that are both structurally and functionally highly divergent (3,4). Within the HSPH (HSP110), HSPA (Hsp70) and DNAJ (HSP40) families, several members have been found that can …show more content…
It under go morphogenesis into a multicellular fruting body by aggregation of cells in that area when faced with starvation thus became popular as a model for study of morphogenesis .In Dictyostelium genome there are number of genes with long CAG repeats. Recently the greatest total content of Q or N runs was found in the social amoeba Dictyostelium discoideum. The CAG repeats in some cases < 40 did not show any pathological condition which is not the case in Yeast and other higher organisms(6) .This leads to the speculation of a cellular mechanism existing in Dictyostelium helping it in alleviate the effects of these CAG repeats . The unusual proteome composition and its experimental accessibility make D. discoideum an ideal organism to study mechanisms that regulate the formation of and the cellular response to protein aggregation, as well as the normal function of Q/N-rich sequences (6).Even though it does not have organization grade required for the study of Neuropathology , it is perfectly suitable for general cellular mechanisms. Along with the above advantages Dictystelium is one of the widely used models to study autophagy and the presence of conserved heat shock proteins makes it suitable to be a model for polyQ diseases. So some of the members from our lab created strains with varying lengths of CAG repeats .These can be used to study the effects of Heat shock protein in poly Q diseases.