TRPM-2/clusterin is induced de novo during the regression of the prostate and other hormone-dependent tissues after hormone ablation, and is over-expressed in several human neurodegenerative diseases including Alzheimer's disease, epilepsy and retinitis pigmentosa.
These data support the hypothesis that overexpression of hsp70i plays an important role in enhancing the survival of neuronal cells following stress and suggests that the induction of a stress response in the CNS may provide an alternative form of treatment for neurodegenerative diseases.
These data support the hypothesis that overexpression of hsp70i plays an important role in enhancing the survival of neuronal cells following stress and suggests that the induction of a stress response in the CNS may provide an alternative form of treatment for neurodegenerative diseases.
On the other hand, the development of spontaneous neurodegenerative disorder in Tg(GSS MoPrP) mice, if independently confirmed, strongly supports the "prion" hypothesis.
Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by expansion of a CAG trinucleotide repeat which codes for glutamine in the protein ataxin-1.
Specifically: (1) transgenic expression of the cytokines IL-6, IL-3 and IFN-alpha in the CNS results in the development of acute (high expression) or chronic progressive (low expression) CNS disease associated with a spectrum of clinical, physiologic and pathologic manifestations; (2) although the clinical, cellular and molecular phenotype produced by the cerebral expression of the various cytokines showed some overlap, the differences were more prominent reflecting the unique actions of each cytokine; (3) these transgenic models which recapitulate many of the structural and functional impairments seen in human neurodegenerative diseases, highlight the point that cytokines, which normally function as primary regulators of the host response, also have the potential to mediate significant injury in the CNS.
The cytokines interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha, produced by glial cells within the brain, appear to contribute to the neuropathogenesis of several inflammatory neurodegenerative diseases; however, little is known about the mechanism underlying cytokine-induced neurotoxicity.
Prion diseases are neurodegenerative disorders that appear to be due to a conformational change, involving the conversion of alpha-helices in the normal, cellular isoform of the prion protein (PrPC) to beta-structure in the infectious scrapie form (PrPSc).
These preliminary data affirm the need for further study of well-characterized cases to explore the relationship of ApoE to cytoskeletal pathology and ND.
Autosomal dominant cerebellar ataxias (ADCA) of type I, a group of clinically heterogeneous neurodegenerative disorders, are known to be genetically heterogeneous since a second locus for ADCA type I (SCA2) has been identified on the long arm of chromosome 12.
We examined apolipoprotein E (ApoE) immunoreactivity and allele frequency in 12 autopsied cases of progressive supranuclear palsy (PSP), a neurodegenerative disease characterized by diffuse neurofibrillary tangle (NFT) formation without beta-amyloid deposits.
The spinocerebellar ataxia 3 locus (SCA3) for type I autosomal dominant cerebellar ataxia (ADCA type I), a clinically and genetically heterogeneous group of neurodegenerative disorders, has been mapped to chromosome 14q32.1.
Batten disease (juvenile-onset neuronal ceroid lipofuscinosis; JNCL) is an autosomal recessive neurodegenerative disorder, characterized by the cytosomal accumulation of autofluorescent proteolipopigments in neurons and other cell types.
Moreover, biochemical studies indicate normal levels of total SOD activity in transgenic mouse tissues, results that indicate that the neurodegenerative disorder does not result from a diminution of activity and, as such, represents a dominant "gain of function" mutation.
Neurotrophic factors, such as ciliary neurotrophic factor (CNTF), have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), a human neurodegenerative disease primarily of upper and lower motor neurones.
Autosomal dominant cerebellar ataxias (ADCA) of type I, a group of clinically heterogeneous neurodegenerative disorders, are known to be genetically heterogeneous since a second locus for ADCA type I (SCA2) has been identified on the long arm of chromosome 12.
Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive neurodegenerative disorder that affects both the central and peripheral nervous systems due to an enzymatic defect of the galactocerebrosidase.
Since Bcl-2 acts strictly on neuronal cell body survival without compensating for nerve degeneration in pmn/pmn/bcl-2 mice, this proto-oncogene would not in itself be sufficient for treatment of neurodegenerative diseases where axonal impairment is a major component.
The spinocerebellar ataxia 3 locus (SCA3) for type I autosomal dominant cerebellar ataxia (ADCA type I), a clinically and genetically heterogeneous group of neurodegenerative disorders, has been mapped to chromosome 14q32.1.
Specifically: (1) transgenic expression of the cytokines IL-6, IL-3 and IFN-alpha in the CNS results in the development of acute (high expression) or chronic progressive (low expression) CNS disease associated with a spectrum of clinical, physiologic and pathologic manifestations; (2) although the clinical, cellular and molecular phenotype produced by the cerebral expression of the various cytokines showed some overlap, the differences were more prominent reflecting the unique actions of each cytokine; (3) these transgenic models which recapitulate many of the structural and functional impairments seen in human neurodegenerative diseases, highlight the point that cytokines, which normally function as primary regulators of the host response, also have the potential to mediate significant injury in the CNS.
The gene for the autosomal recessive neurodegenerative disorder spinal muscular atrophy has been mapped to a region of 5q13 flanked proximally by CMS-1 and distally by D5S557.