Indian scientists find missing link in body’s cells to boost therapies for Alzheimer’s, cancer

New Delhi, Dec 19 Researchers from the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) have uncovered a surprising player in autophagy, or the “self-eating” process that removes damaged parts of cells that can pave the way for developing therapies for diseases such as Alzheimer’s, Parkinson's, and cancer.

Autophagy is a key biological process where cells clear out damaged and unwanted materials. When a cell fails to clear waste, its health suffers, especially in long-lived neurons. The autophagy pathway, which removes damaged material and defends against infections, is disrupted in diseases like Alzheimer’s and Huntington’s.

In cancer, autophagy plays dual roles. Autophagy initially prevents cancer but later supports tumour growth. Autophagy also acts as a tumour suppressor by maintaining genome integrity and cellular homeostasis by clearing cellular junk such as protein aggregates and damaged mitochondria.

But it is also a double-edged sword as certain types of cancer cells hijack autophagy for their own survival and propagation. Understanding its regulation is crucial for the development of effective therapies.

The team from JNCASR, an autonomous institution under the Department of Science and Technology (DST), found that a group of proteins called the exocyst complex, which normally helps move important molecules to the cell surface, also plays a key role in autophagy.

This complex comprises a team of 8 proteins; interestingly, 7 of the 8 proteins are required to help the cell grow the trash bag so that it can completely wrap up the waste. When this complex is missing, the cell’s bag-making factory stops working properly and even starts producing faulty, non-functional factories.

The researchers led by Prof. Ravi Manjithaya used simple yeast cells to elucidate the formation of autophagosomes (cellular “trash bags”), thereby providing insights into how this vital process operates in higher organisms.

They elucidated the mechanism by which a protein complex, exocyst, previously recognised for its role in secretion, also contributes to the autophagy pathway, which is crucial for maintaining cellular health.

Since defects in autophagy are linked to several neurodegenerative diseases and cancers, the findings published in the journal Proceedings of the National Academy of Sciences will open new avenues for modulating this pathway to restore cellular balance and develop potential therapeutic.

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