The lysosomal
cysteine protease enzyme, named
Cathepsin B, mainly degrades the
protein and manages its average turnover in our body. The
Cathepsin B active form is mostly present inside the lysosomal part at a cellular level, providing the slightly acidic medium for its activation. Multiple findings on
Cathepsin B reveal its involvement in neurons' degeneration and a possible role as a neuronal death mediator in several
neurodegenerative diseases. In this review article, we highlight the participation of
Cathepsin B in the etiology/progress of AD, along with various other factors. The
enzyme is involved in producing neurotoxic Aβ
amyloid in the AD brain by acting as the β-
secretase enzyme in the regulated secretory pathways responsible for APP processing. Aβ
amyloid accumulation and
amyloid plaque formation lead to neuronal degeneration, one of the prominent pathological hallmarks of AD.
Cathepsin B is also involved in the production of PGlu-Aβ, which is a truncated and highly neurotoxic form of Aβ. Some of the findings also revealed that
Cathepsin B specific gene deletion decreases the level of PGlu-Aβ inside the brain of experimental mice. Therefore, neurotoxicity might be considered a new pathological indication of AD due to the involvement of
Cathepsin B. It also damages neurons present in the CNS region by producing inflammatory responses and generating mitochondrial ROS. However,
Cathepsin B inhibitors, i.e.,
CA-074, can prevent neuronal death in AD patients. The other natural inhibitors are also equally effective against neuronal damage with higher selectivity. Its synthetic inhibitors are specific for their target; however, they lose their selectivity in the presence of quite a few
reducing agents. Therefore, a humanized
monoclonal antibody is used as a selective
Cathepsin B inhibitor to overcome the problem experienced. The use of
Cathepsin B for the treatment of AD and other
neurodegenerative diseases could be considered a rational therapeutic target.