BIOTECHNOLOGY
Figure 1: Promising kinase targets and converging pathways in neurodegenerative diseases. Figure source:
https://doi.org/10.3389/fnagi.2020.00242
MANAGING SCARCITY
Here, biotechnology company Sino Biological explores kinase inhibitors and how they promise impressive therapeutics for neurodegenerative diseases
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eurodegenerative diseases like Alzheimer’s (AD), Parkinson’s (PD), and amyotrophic lateral
sclerosis (ALS) suffer from a scarcity of effective treatments. Current therapies primarily provide symptomatic relief but do not address the underlying pathology, failing to slow or halt disease progression. This underscores the urgent need to identify new therapeutic targets relevant to the pathology of these conditions. Kinases represent highly tractable drug targets, with kinase inhibitors achieving
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significant success, particularly in oncology. However, their potential in neurodegenerative diseases remains largely unexplored, presenting a promising avenue for future research and therapeutic development. The rationale for targeting kinases
in central nervous system (CNS) drug discovery is based on the understanding that phosphorylation, catalysed by kinases, plays a pivotal role in regulating many cellular processes, and that at least a number of phosphorylation processes may become aberrant in disease (Figure 1). Over the past decade, there
has been an increasing interest in the therapeutic potential of brain penetrant kinase inhibitors for neurodegenerative diseases. The development of kinase inhibitors, such as glycogen synthase kinase-3β (GSK- 3β) inhibitors for AD, leucine-rich repeat kinase 2 (LRRK2) inhibitors for PD, and mitogen-activated protein kinase kinase kinase kinase (MAP4K) inhibitors for ALS, has shown promise, though challenges like specificity, blood-brain barrier penetration, and drug resistance remain.
THE ROLE OF KINASES IN NEURODEGENERATIVE DISEASES Kinases are integral to the regulation of signaling pathways in the brain, and alterations in their function are implicated in neurodegeneration. In neurodegenerative diseases, certain kinases are often overactive or overexpressed in specific brain regions. This dysregulation frequently drives the hyperphosphorylation of proteins that are prone to aggregation, such as tau in AD, α-synuclein in PD, and TDP-43 in ALS. Moreover, aberrant kinase signaling can also induce other disease- promoting phenotypes, including
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