Chaperons also known as retromer protein complex could help treat Alzheimer's disease, say researchers.
Retromer plays a vital role in neurons, steering amyloid precursor protein (APP) away from a region of the cell where APP is cleaved, creating the potentially toxic byproduct amyloid-beta, which is thought to contribute to the development of Alzheimer's.
Alzheimers Disease
Alzheimer''s disease is a progressive neurodegenerative disease affecting memory and thinking and making the person increasingly dependent on others.
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Using computer-based virtual screening, the researchers identified a new class of compounds, called pharmacologic chaperones that can significantly increase retromer levels and decrease amyloid-beta levels in cultured hippocampal neurons, without apparent cell toxicity.
Dagmar Ringe, PhD, Harold and Bernice Davis Professor in the Departments of Biochemistry and Chemistry, said their challenge was to find small molecules-or pharmacologic chaperones-that could bind to retromer's weak point and stabilize the whole protein complex.
![Quiz On Alzheimer’s Disease]( "Quiz On Alzheimer’s Disease")
Alzheimer's disease (AD) is the most common form of dementia. Participate in this quiz to find out how much you know about this debilitating disease.
This was accomplished through computerized virtual, or in silico, screening of known chemical compounds, simulating how the compounds might dock with the retromer protein complex. (In conventional screening, compounds are physically tested to see whether they interact with the intended target, a costlier and lengthier process.)
The screening identified 100 potential retromer-stabilizing candidates, 24 of which showed particular promise. Of those, one compound, called R55, was found to significantly increase the stability of retromer when the complex was subjected to heat stress.
The researchers then looked at how R55 affected neurons of the hippocampus, a key brain structure involved in learning and memory.
More important, a subsequent experiment showed that the compound significantly increased retromer levels and decreased amyloid-beta levels in cultured neurons taken from healthy mice and from a mouse model of Alzheimer's. The researchers are currently testing the clinical effects of R55 in the actual mouse model.
The study has been published online in the journal Nature Chemical Biology.
Source: ANI
Quiz On Alzheimer’s Disease
Alzheimer's disease (AD) is the most common form of dementia. Participate in this quiz to find out how much you know about this debilitating disease.
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This was accomplished through computerized virtual, or in silico, screening of known chemical compounds, simulating how the compounds might dock with the retromer protein complex. (In conventional screening, compounds are physically tested to see whether they interact with the intended target, a costlier and lengthier process.)
The screening identified 100 potential retromer-stabilizing candidates, 24 of which showed particular promise. Of those, one compound, called R55, was found to significantly increase the stability of retromer when the complex was subjected to heat stress.
The researchers then looked at how R55 affected neurons of the hippocampus, a key brain structure involved in learning and memory.
More important, a subsequent experiment showed that the compound significantly increased retromer levels and decreased amyloid-beta levels in cultured neurons taken from healthy mice and from a mouse model of Alzheimer's. The researchers are currently testing the clinical effects of R55 in the actual mouse model.
The study has been published online in the journal Nature Chemical Biology.
Source: ANI
Modified Stem Cells Offer Potential Pathway to Treat Alzheimer's Disease
Genetically modified neural stem cells show effective results when transplanted into the brains of mice with Alzheimer's disease symptoms, says study.
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 Women at Higher Risk of Alzheimer's Than Men Due to a Gene Variant: StudyWomen are at a greater risk for Alzheimer's disease than men because they are found to carry a copy of a gene variant called ApoE4, reveals a new study. | Advertisement
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