Neuroscience 2002 Abstract
| Presentation Number: | 692.1 |
|---|---|
| Abstract Title: | Isomorphic Recruitment in Neurodegenerative Diseases. |
| Authors: |
Griffin, J. K.*1
; Sehgal, S.1
; Cashman, N. R.1
1Ctr Res Neuro Diseases, Univ Toronto, Toronto, Canada |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Neurodegenerative Disorders -- Prion Diseases |
| Secondary Theme and Topics | Neurological and Psychiatric Conditions<br />- Neurodegenerative Disorders<br />-- ALS |
| Session: |
692. Neurodegenerative disorders: prion diseases Poster |
| Presentation Time: | Wednesday, November 6, 2002 8:00 AM-9:00 AM |
| Location: | Hall A2-B3 Y-1 |
| Keywords: | NEURODEGENERATION, ALS, SUPEROXIDE DISMUTASE, AMYLOID |
Many sporadic and familial neurodegenerative diseases are associated with neural protein deposits. We have recently reported (Griffin et al, SFN Abs 2001) that familial prion diseases appear to respect an allele barrier, such that conservativeness of missense substitutions governs whether multimer accretion of PrP is restricted to mutant protein only (slowly progressive disease), or from protein encoded by both the mutant and wild-type alleles (rapidly progressive disease). We now investigate if a similar model might apply to other neurodegenerative diseases characterized by protein aggregation, such as amyotrophic lateral sclerosis (ALS) and familial amyloidotic polyneuropathy (FAP), associated with mutations in superoxide (SOD1) and transthyretin (TTR) genes respectively. Using the Bacon and BLOSUM 62 indices of amino acid similarity (Bacon and Anderson, 1986; Henikoff and Henikoff, 1992) we evaluated the pathogenic missense mutations in SOD1 and TTR and compared these to the clinical data. In both diseases, more rapid progression was associated with conservative mutations, suggesting the existence of a prion-like allele barrier in fALS and FAP. A similar process may also apply to sporadic forms of these diseases in which aggregates (seeded by stochastic misfolding or somatic mutation) are rapidly propagated by protein encoded by two wild-type alleles. Our findings suggest that features of the prion hypothesis - including structure-sensitivity and substrate concentration-dependence - might be generally applicable to other post-translational disorders of the proteome. We propose that this pathological process of protein aggregation be designated isomorphic recruitment..
Supported by Caprion Pharma
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2002 Neuroscience Meeting Planner. Orlando, FL: Society for Neuroscience, 2002. Online.
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