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Neuromelanin organelles are specialized autolysosomes that accumulate undegraded proteins and lipids in aging human brain and are likely involved in Parkinson’s disease.


Maximus Peto’s Commentary

This group reports that neuromelanin precursors appear to be degraded relatively slowly in neurons, and suggest that neuromelanin accumulation may contribute to Parkinson’s.


Neuromelanin organelles are specialized autolysosomes that accumulate undegraded proteins and lipids in aging human brain and are likely involved in Parkinson’s disease.
NPJ Parkinsons Dis. 2018 Jun 5;4:17.
Zucca FA#, Vanna R#, Cupaioli FA, Bellei C, De Palma A, Di Silvestre D, Mauri P, Grassi S, Prinetti A, Casella L, Sulzer D, Zecca L
DOI: 10.1038/s41531-018-0050-8
PubMed publication date (edat): 6/15/2018

Abstract

During aging, neuronal organelles filled with neuromelanin (a dark-brown pigment) and lipid bodies accumulate in the brain, particularly in the substantia nigra, a region targeted in Parkinson’s disease. We have investigated protein and lipid systems involved in the formation of these organelles and in the synthesis of the neuromelanin of human substantia nigra. Membrane and matrix proteins characteristic of lysosomes were found in neuromelanin-containing organelles at a lower number than in typical lysosomes, indicating a reduced enzymatic activity and likely impaired capacity for lysosomal and autophagosomal fusion. The presence of proteins involved in lipid transport may explain the accumulation of lipid bodies in the organelle and the lipid component in neuromelanin structure. The major lipids observed in lipid bodies of the organelle are dolichols with lower amounts of other lipids. Proteins of aggregation and degradation pathways were present, suggesting a role for accumulation by this organelle when the ubiquitin-proteasome system is inadequate. The presence of proteins associated with aging and storage diseases may reflect impaired autophagic degradation or impaired function of lysosomal enzymes. The identification of typical autophagy proteins and double membranes demonstrates the organelle’s autophagic nature and indicates that it has engulfed neuromelanin precursors from the cytosol. Based on these data, it appears that the neuromelanin-containing organelle has a very slow turnover during the life of a neuron and represents an intracellular compartment of final destination for numerous molecules not degraded by other systems.

PMID: 29900402
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988730/

Maximus Peto

Max Peto is a longevity researcher and founder of Long Life Labs. A biochemist by training, he studies the biochemistry of aging and longevity and has worked with research organizations such as SENS Research Foundation, Methuselah Foundation, BioAge Labs, Life Extension Foundation, and Ichor Therapeutics. His work at Long Life Labs is focused on empowering people to understand and manage the most critical factors for better health and longer life.

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