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Human enzyme may help find cure for Alzheimer's disease

New York: Scientists have identified a human enzyme that can unravel protein aggregates the hallmark of a number of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.

The study said that the finding can help develop new therapeutic strategy for these diseases.

An experimental expression of the human enzyme known as cyclophilin 40 or CyP40, was found to preserve brain neurons and rescued cognitive deficits in a mouse model.

The enzyme has also disaggregated alpha-synuclein, an aggregate associated with Parkinson's disease.

This is the first time that CyP40 has been shown to disaggregate an amyloid responsible for a neurodegenerative disease.

Laura Blair, from the University of South Florida said, "The finding that Cyp40 can untangle clumps of tau and alpha-synuclein suggests that it, or one of the more than 40 other human proteins with similar activity, may have a role to play in treating neurodegenerative disease."

In most neurodegenerative diseases, misfolded proteins aggregate to form an insoluble clump called amyloid. Many amyloid-forming proteins, including tau in Alzheimer's disease and alpha-synuclein in Parkinson's disease, contain the amino acid proline, whose unique structure induces a bend in the amino acid chain.

Those bends contribute to stacking of adjacent regions of the protein, thus promoting amyloid formation.

During normal protein folding, CyP40 latches on to prolines, orienting them into their characteristic chain-bending conformation, but like most enzymes, it can also operate in reverse, helping to unbend the chain.

Researchers said, understanding more about the exact mechanism of the enzyme may help point toward a therapeutic strategy centered on proline's role in amyloid formation.

The study was published in the journal PLOS Biology.

June 28, 2017


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