It is known that cells can transfer mitochondria from one to another under some circumstances, and here researchers demonstrate that they can transfer lysosomes as well. The lysosomes in a cell play the role of recycling units, breaking down damaged structures and waste proteins. Unfortunately there are some forms of waste that our biochemistry cannot manage, and these compounds accumulate over time into a harmful mix called lipofuscin. In old tissues, long-lived cells have clogged and malfunctioning lysosomes, unable to perform the task of recycling waste. This spirals downwards into a garbage catastrophe and the cells either die or become highly dysfunctional themselves. This process of resilient waste accumulation in lysosomes is one of the root causes of aging and age-related disease.
The research here focuses on just one form of damaged protein and one class of conditions caused by the accumulation of that protein, but the transfer of lysosomes noted by the researchers has broad implications for the more general process of lysosomal dsyfunction in aging. If cells are transferring lysosomes in all tissues then this will act to dilute damage for the worst affected cells at the cost of spreading the damage more widely within important cell populations - it will be an important determinant of the way in which damage and decline progresses. That said, this is of interest but not importance given a class of therapy that can break down the waste that makes up lipofuscin. With such a tool, capable of delivering suitable enzymes to the lysosome, it doesn't matter how the waste material spreads. The SENS Research Foundation has been working on this for a while now, mining the bacterial world for suitable enzymes. Some of these have been licensed to Human Rejuvenation Technologies, and others to Ichor Therapeutics for further development for specific therapies.
Synucleinopathies, a group of neurodegenerative diseases including Parkinson's disease, are characterized by the pathological deposition of aggregates of the misfolded α-synuclein protein into inclusions throughout the central and peripheral nervous system. Intercellular propagation (from one neuron to the next) of α-synuclein aggregates contributes to the progression of the neuropathology, but little was known about the mechanism by which spread occurs. In this study researchers used fluorescence microscopy to demonstrate that pathogenic α-synuclein fibrils travel between neurons in culture, inside lysosomal vesicles through tunneling nanotubes (TNTs), a new mechanism of intercellular communication.
After being transferred via TNTs, α-synuclein fibrils are able to recruit and induce aggregation of the soluble α-synuclein protein in the cytosol of cells receiving the fibrils, thus explaining the propagation of the disease. The scientists propose that cells overloaded with α-synuclein aggregates in lysosomes dispose of this material by hijacking TNT-mediated intercellular trafficking. However, this results in the disease being spread to naive neurons. This study demonstrates that TNTs play a significant part in the intercellular transfer of α-synuclein fibrils and reveals the specific role of lysosomes in this process. This represents a major breakthrough in understanding the mechanisms underlying the progression of synucleinopathies. These compelling findings, together with previous reports from the same team, point to the general role of TNTs in the propagation of prion-like proteins in neurodegenerative diseases and identify TNTs as a new therapeutic target to combat the progression of these incurable diseases.