Inhibition of cathepsin X as a novel strategy for the treatment of neuroinflammation-associated diseases
2021
Тип документа:
Конференцијски прилог (Објављена верзија)
,
© 2021 The Authors. FEBS Open Bio
Метаподаци
Приказ свих података о документуАпстракт:
Inflammation is closely implicated in the pathogenesis of several
neurodegenerative disorders, including Parkinson’s disease (PD) and multiple sclerosis (MS), where the hallmark of neuroinflammation
is activated microglia. Microglia-derived lysosomal
cathepsins have been increasingly recognized as important inflammatory
mediators that trigger signalling pathways that aggravate
neuroinflammation. In the past, a contribution to neuroinflammation
processes has been shown for cathepsin X in vitro, however;
the expression patterns and functional roles of cathepsin X
in neuroinflammatory brain pathology remained elusive. Our
recent studies revealed a strong neuroinflammation-induced
upregulation of cathepsin X expression and activity using in vivo
models that mimic the pathology of PD and MS, respectively.
Unilateral injection of lipopolysaccharide into the rat striatum
induced strong upregulation of cathepsin X expression and its
activity in the ipsilateral striatum and in other brain areas such
as cerebral cortex, corpus callosum, subventricular zone and
external globus pallidus, whereas the upregulation was mainly
restricted to activated microglia and reactive astrocytes. Similarly,
a marked increase in expression and activity of cathepsin X
was observed in spinal cord in rat model of experimental autoimmune
encephalomyelitis. Additionally, cathepsin X upregulation
was observed in injured peripheral nerve, localized in the inflammatory
cell type, M1 macrophages. Nevertheless, continuous
administration of the cathepsin X inhibitor showed moderate
protective effects against neuroinflammation-induced degeneration;
further indicating that cathepsin X plays a role as a pathogenic
factor in neuroinflammation-induced neurodegeneration
and represents a potential therapeutic target for neurodegenerative
diseases associated with inflammation.
У:
- 45th FEBS Congress: Molecules of Life: Towards New Horizons; 2021 Jul 3-8; Ljubljana, Slovenia. Hoboken: Wiley; 2021. p. 59-60.