New antibody discovery platform delve deeper into Alzheimer, Parkinson says researchers

By Anjali Sharma

NEW YORK – According to researchers on Monday a new antibody discovery platform can delve deeper into the mechanisms underlined the processes behind Alzheimer’s and Parkinson’s diseases.

Parkinson’s and Alzheimer’s, specific proteins misfold and clump together, forming toxic aggregates that damage brain cells, the researchers said.

The process of proteins spontaneously clumping is called protein aggregation and researchers have developed novel methods to generate aggregate-specific antibodies as specific probes or modulators of the aggregation process.

The new method overcomes significant challenges in characterizing these complex and often transient protein structures, the study said.

The antibodies, known for their precise target binding, offer a powerful tool for investigating these structures, but generating antibodies against such transitory targets has been a major hurdle.

It integrates computational design and directed evolution to develop new antibodies, which are then screened for their ability to bind to target aggregates or inhibit aggregation process.

Francesco Aprile, PhD, Associate Professor in Biological Chemistry at Imperial College London led the study said “We can substantially speed up the process of discovery and production, which can save time and resources”.

Aprile and colleagues successfully generated single-domain antibodies (nanobodies) targeting intrinsically disordered proteins, or proteins that are not defined by one specific three-dimensional structure, but that are constantly changing.

“What these intrinsically disordered proteins do is they start to self-assemble and form oligomers and aggregates such as amyloid fibrils, which are a hallmark of Alzheimer’s,” Aprile noted.

The nanobodies the researchers developed can target different assemblies of amyloid-beta and alpha-synuclein, proteins associated with Alzheimer’s and Parkinson’s diseases.

These nanobodies can provide valuable insights into what makes these proteins form toxic oligomers.

“Our platform represents a significant advance in our ability to study protein self-assembly,” said Aprile.

“By efficiently generating nanobodies against these challenging targets, we can now delve deeper into the mechanisms underlying these processes and their role in disease.”

The research has identified specific regions within amyloid-beta and alpha-synuclein that could be promising therapeutic targets.

The discovery opens new avenues for drug development aimed at treating Alzheimer’s and Parkinson’s, it said.

Aprile said by targeting these key protein assemblies, we may be able to slow or even prevent disease progression.

The Biophysical Society has been established to lead development and dissemination of knowledge in biophysics.