Tags

Type your tag names separated by a space and hit enter

Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease.
Nat Med. 1998 Nov; 4(11):1318-20.NMed

Abstract

Two mutations in the gene encoding alpha-synuclein have been linked to early-onset Parkinson's disease (PD). alpha-Synuclein is a component of Lewy bodies, the fibrous cytoplasmic inclusions characteristic of nigral dopaminergic neurons in the PD brain. This connection between genetics and pathology suggests that the alpha-synuclein mutations may promote PD pathogenesis by accelerating Lewy body formation. To test this, we studied alpha-synuclein folding and aggregation in vitro, in the absence of other Lewy body-associated molecules. We demonstrate here that both mutant forms of alpha-synuclein (A53T and A30P) are, like wild-type alpha-synuclein (WT), disordered in dilute solution. However, at higher concentrations, Lewy body-like fibrils and discrete spherical assemblies are formed; most rapidly by A53T. Thus, mutation-induced acceleration of alpha-synuclein fibril formation may contribute to the early onset of familial PD.

Authors+Show Affiliations

Center for Neurologic Diseases, Brigham and Women's Hospital and Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

9809558

Citation

Conway, K A., et al. "Accelerated in Vitro Fibril Formation By a Mutant Alpha-synuclein Linked to Early-onset Parkinson Disease." Nature Medicine, vol. 4, no. 11, 1998, pp. 1318-20.
Conway KA, Harper JD, Lansbury PT. Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease. Nat Med. 1998;4(11):1318-20.
Conway, K. A., Harper, J. D., & Lansbury, P. T. (1998). Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease. Nature Medicine, 4(11), 1318-20.
Conway KA, Harper JD, Lansbury PT. Accelerated in Vitro Fibril Formation By a Mutant Alpha-synuclein Linked to Early-onset Parkinson Disease. Nat Med. 1998;4(11):1318-20. PubMed PMID: 9809558.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease. AU - Conway,K A, AU - Harper,J D, AU - Lansbury,P T, PY - 1998/11/11/pubmed PY - 2001/3/23/medline PY - 1998/11/11/entrez SP - 1318 EP - 20 JF - Nature medicine JO - Nat Med VL - 4 IS - 11 N2 - Two mutations in the gene encoding alpha-synuclein have been linked to early-onset Parkinson's disease (PD). alpha-Synuclein is a component of Lewy bodies, the fibrous cytoplasmic inclusions characteristic of nigral dopaminergic neurons in the PD brain. This connection between genetics and pathology suggests that the alpha-synuclein mutations may promote PD pathogenesis by accelerating Lewy body formation. To test this, we studied alpha-synuclein folding and aggregation in vitro, in the absence of other Lewy body-associated molecules. We demonstrate here that both mutant forms of alpha-synuclein (A53T and A30P) are, like wild-type alpha-synuclein (WT), disordered in dilute solution. However, at higher concentrations, Lewy body-like fibrils and discrete spherical assemblies are formed; most rapidly by A53T. Thus, mutation-induced acceleration of alpha-synuclein fibril formation may contribute to the early onset of familial PD. SN - 1078-8956 UR - https://www.unboundmedicine.com/medline/citation/9809558/Accelerated_in_vitro_fibril_formation_by_a_mutant_alpha_synuclein_linked_to_early_onset_Parkinson_disease_ L2 - https://doi.org/10.1038/3311 DB - PRIME DP - Unbound Medicine ER -