Research groups at TIFR, Mumbai, IISc, Bangalore and the University of
Toronto working together, may have gotten the closest yet to figuring
out how the toxic form of the Alzheimer’s molecule looks. Alzheimer’s disease is a progressive form of dementia that is
characterised by loss of short-term memory, deterioration in behaviour
and intellectual performance, besides slowness of thought. It may occur
in middle age or in old age, and while a lot of research is on for drug
treatments, none has been successful.
While it is widely accepted that a specific form of the Amyloid beta
molecule is a major player in causing Alzheimer’s, the shape and form of
this remained elusive, experts say. The excitement now is that
scientists have caught a glimpse of the molecule during its attempt to
enter a cell membrane, using a new method involving laser light and
fat-coated silver nanoparticles. “It is a rare protein and is difficult to probe. It was slightly
fortuitous that we found it, using a modified version of Raman
Spectroscopy. Usually the signal from this is weak, but we mimicked the
cell’s outer layer by encasing silver nanoparticles in a fat membrane,”
says Sudipta Maiti, of TIFR, who co-directed the research with P.K.
Madhu. The Amyloid beta molecules were fooled into piercing this
‘membrane’ and the nanoparticles enhanced the signals, allowing
scientists to see it at that point. When proteins aggregate, or gang up to form a structure, they shift
shapes. “At some stage of ganging up they suddenly start attacking the
cell membrane and that’s where toxicity begins. How they enter the
membrane, and what they look like when entering the membrane is key,” he
says.
The ‘lock’ looks like a bunch of Amyloid beta molecules each in the
shape of a hairpin, but with a twist, TIFR has said in a release.
Debanjan Bhowmik, the lead contributor of the study, says “This has been
suspected earlier, but what we found was an unexpected twist in the
structure, now becoming a beta-hairpin — very different from the typical
hairpin structure people imagined.” This technique might also help in
finding the shape of similar proteins in future, Dr. Maiti adds.
The findings were published in the journal ACS Nano this week.
If indeed it turns out to be the ‘lock’ for Alzheimer’s then the
discovery will facilitate new efforts to finding a key — an intelligent
drug candidate designed to attack the lock. “We have been working on the
project for nearly 12 years now, and it is only now that we have
started working with a few colleagues from the Institute of Chemical
Technology who have the expertise in the field of intelligent design of
drug molecules,” Dr. Maiti says.
“The use of technology to identify peptides and peptide transformations,
which helps us understand the structure in great detail, is important —
both for definitive diagnosis and definitive treatments. Once defined,
researchers could adopt the technique to study wider samples, and this
will lead to a greater understanding and modification of processes,
eventually to better clinical care,” says Ennapadam S. Krishnamoorthy,
Chennai-based senior neuropsychiatrist, and founder, Neurokrish.
source-The Hindu
