Neurodegenerative diseases familial

Lewy bodies, neurofibrillary lesions and Pick bodies are intracellular filamentous inclusions. It is now well established that Lewy bodies are made of the protein a-synuclein and both neurofibrillary lesions and Pick bodies of the microtubule-associated protein tau. Mutations in the a-synuclein gene or an increase in its copy number cause autosomal-dominantly inherited forms of Parkinson s disease and dementia with Lewy bodies. Mutations in the tau gene cause a familial form of frontotemporal dementia. Here we review the evidence implicating a-synuclein and tau in these inherited and a number of sporadic neurodegenerative diseases. Collectively, a-synucleinopathies and tauopathies account for the vast majority of cases of late-onset neurodegenerative disease (Tables 45-1 and 45-2). 

Lee, M.K. et al. Human a-synuclein-harboring familial Parkinson s disease-linked Ala-53 to Thr mutation causes neurodegenerative disease with a-synuclein aggregation in transgenic mice. Proc. Natl. Acad. Sci. USA 99 8968-8973, 2002. 

Sherman, M. Y., Goldberg, A. L. 2001. Cellular defenses against unfolded proteins a cell biologist thinks about neurodegenerative diseases. Neuron 29 15-32. Shimura, H., Hattori, N., Kubo, S., Mizuno, Y., Asakawa, S., et al. 2000. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet 25 302-5. 

Limited clinical success keeps optimism alive that neurotrophic factors will find application in the treatment of some neurodegenerative disease. However, no member of this family of regulatory proteins have been approved for medical use, despite all the clinical investigations undertaken over the last decade and a half... 

In earlier investigations by the author (3), oxamyl dipeptide derivatives, (I), were prepared, which were effective as ICE/ced-3 family inhibitors, and used in treating the patients suffering from inflammatory, autoimmune, and neurodegenerative diseases. 

We have been studying the E.coli expression of human neurotrophin-3 (NT-3), a member of the nerve growth factor (NGF) family of neurotrophic factors. The protein is believed to have value in the treatment of certain neurodegenerative diseases (6). Mature NT-3 is a polypeptide of 119 amino acid residues and under physiological conditions, the protein functions as a tightly associated, noncovalently liiiked homodimer. Expression of NT-3 using UAA or UAG as the... 

Familial Neurodegenerative Diseases and Single Nucleotide Polymorphisms... 

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