Study Finds Connection between Lysosomes and Neurodegenerative Diseases

Aug, 2021 - By SMI

A team of researchers from the Institute Pasteur (Paris) and the French National Centre for Scientific Research studied the connection of lysosomes in spreading Parkinson's disease.

Neurodegenerative diseases is one of the leading causes of death globally over the past few decades. Researchers around the world are trying to understand the pathogenesis associated with neurodegenerative diseases. They are making strong efforts to develop effective therapeutics for these incurable neurodegenerative diseases. However, the researchers believe that they still fail to understand the complete molecular mechanisms associated with the neurodegenerative diseases. In this study, researchers tried to unfold the connection of lysosomes in spreading Parkinson's disease. They explained α-synuclein fibrils transfer from donor to acceptor cells through tunneling nanotubes. α-synuclein is a protein that is abundant in brain and regulates synaptic vesicle trafficking and neurotransmitter release. The researchers observed that these α-synuclein fibrils are transferred through tunneling nanotubes inside lysosomes. Lysosomes are membrane-bound organelles which is responsible for degrading and recycling cellular waste. Moreover, defects in genes encoding lysosomal proteins is responsible for causing lysosomal storage disorders. The researchers found that α-synuclein fibrils can modify shape of lysosomes and allow diffusion and seeding. They found that α-syn fibrils affect the structure of lysosomes and decrease their function in neuronal cells by using super-resolution and electron microscopy. For instance, in Parkinson’s disease which is the most common neurodegenerative disease, misfolded α-synuclein proteins assemble in fibrillar aggregates within neurons.

In a nutshell, the team found that α-syn fibrils make the peripheral re-distribution of the lysosomes. They also revealed that α-syn fibrils can reduce the degrading characteristics of lysosomes and allow seeding of soluble α-syn that takes place only in those lysosomes. This discovery can be used for developing novel therapeutics to target neurodegenerative diseases.