Lysosomal Dysfunction and the Death of Neurons via Ferroptosis

Here find supporting evidence for the SENS view of lipofuscin and lysosomal dysfunction in aging. Lysosomes are the recycling units of the cell, packed with enzymes to break down unwanted structures and molecules into raw materials. Over time, long-lived cells such as the neurons of the central nervous system are negatively affected by the build up of resilient metabolic waste that is challenging to break down. Collectively this waste is called lipofuscin, but it contains many different problem compounds, and overall is poorly catalogued. Lysosomes in old neurons are observed to be bloated and dysfunctional, leading to cells that become overtaken with broken machinery that cannot be recycled. As noted here, the end result is cell death, and an accelerated pace of neural cell death is the road to neurodegenerative conditions. A toxic brew of lysosomal lipids, reactive iron atoms, and oxidative stress can spell doom for human neurons. This is the upshot of the first-ever CRISPR screens at the genome-wide level in these cells. Researchers used the genome-editing tool to dial up or down expression of each protein-coding gene in the human neuronal genome. They uncovered a surprising connection between endolysosomal processing and the iron-dependent cell-death pathway called ferroptosis. Zeroing in on that pathway, the researchers found that in the absence of the lysosomal protein prosaposin (PSAP), glycosphingolipids accumulate in the lysosomes, setting off oxidati...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs