Both Familial Parkinson's Disease Mutations Accelerate α-Synuclein Aggregation

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Mutations associated with familial Parkinson's disease alter the initiation and amplification steps of α-synuclein aggregation.

Parkinson's disease is a highly debilitating neurodegenerative condition whose pathological hallmark is the presence in nerve cells of proteinacious deposits, known as Lewy bodies, composed primarily of amyloid fibrils of α-synuclein. Several missense mutations in the gene encoding α-synuclein have been associated with familial variants of Parkinson's disease and have been shown to affect the k...

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Familial Parkinson disease mutations influence α-synuclein assembly.

Lewy bodies composed of aggregates of α-synuclein (αS) in the brain are the main histopathological features of Lewy body diseases (LBD) such as Parkinson's disease and dementia with Lewy bodies. Mutations such as E46K, A30P and A53T in the αS gene cause autosomal dominant LBD in a number of kindreds. Although these mutations accelerate fibril formation, their precise effects at early stages of ...

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Models of α-synuclein aggregation in Parkinson’s disease

Parkinson's disease (PD) is not only characterized by motor disturbances but also, by cognitive, sensory, psychiatric and autonomic dysfunction. It has been proposed that some of these symptoms might be related to the widespread pathology of α-synuclein (α-syn) aggregation in different nuclei of the central and peripheral nervous system. However, the pathogenic formation of α-syn aggregates in ...

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α-Synuclein Misfolding and Aggregation in Parkinson’s Disease

Parkinson’s disease (PD) is a fatal neurodegenerative disorder that affects 1.5 millions Americans and 1 in 100 individuals over the age of 60. It results from neuronal atrophy localized within the substantia nigra pars compacta. Upon autopsy, PD patients have large intraneuronal fibrils, Lewy Bodies, composed of αsynuclein. Familial forms of PD result from the A30P and A53T mutations within α-...

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Huntington's and Parkinson's diseases are neurodegenerative disorders associated with unusual protein interactions. Although the origin and evolution of these diseases are completely different, characteristic deposits of protein aggregates (huntingtin and α-synuclein resp.), are a common feature in both diseases. After these observations, many studies are performed with both proteins. Some of t...

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 1999

ISSN: 0021-9258

DOI: 10.1074/jbc.274.14.9843