Role and Molecular Mechanisms of Lysosomes and Cathepsins in Neuropathology and Aging: New Insights

Khawar Muhammad Babar,Amaan Hafiza Nabeela,Arif Amin,Siddique Zerwa,Sheikh Nadeem,Farooq Adil,Mukhtar Maryam,Fatima Naz,Ahmad Zaira,Abbasi Muddasir Hassan,Mehmood Rabia,Saeed Tahaa

doi:10.36959/459/605

Khawar Muhammad Babar, Amaan Hafiza Nabeela + Show 10 more

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Lysosomes are the major catabolic machinery that degrades several biomolecules and pathogens. They do so by a vast assortment of their cathepsins and help in maintaining homeostasis. Cathepsins and their variants are reported to be involved in multiple physiological activities including apoptosis, coagulation, cell proliferation, immunity, and digestion, etc. Here, we have reviewed the role of lysosomes and cathepsins in various nervous system pathologies and aging. Moreover, we have provided an insightful approach that by targeting these cathepsins may promise better future therapies to improve not only the life span but also the healthspan.

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Lysosomes, single membrane-bounded organelles, are characterized as major catabolic entities and have been reported in all types of animal cells except red blood cells (RBCs)
Translocation of cathepsin D from the lysosome to cytosol leads to cell death in the aged brain [44]
The survival of an organism is governed by its capability to sustain a balance between the production of new stuff and the degradation of old harmful cellular structures. This balance is strictly controlled by catabolic capacity of the cell, which is accomplished by two processes: 1) Ubiquitin/proteasomal degradation pathway, mainly targets cytosolic and endoplamic reticulum (ER) proteins following their retrograde transport to the cytosol while ubiquitinated mitochondrial proteins are exposed [62,63], 2) Autophagic machinery destroys cytosolic substrates, from single proteins to whole organelles which are delivered to the lysosome for hydrolytic damage

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Single membrane-bounded organelles, are characterized as major catabolic entities and have been reported in all types of animal cells except red blood cells (RBCs). Brain, Cathepsins, Healthspan, Life span, Lysosomes, Neurodegeneration, Neurons A significantly decreased level of cathepsin L has been observed in the brain of aged rats.

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