Role of Enzymes in Disease Mechanisms, Particularly in Neurodegeneration

Kevin Francesco, Department of Pharmacology, Yale University, New Haven, USA, Email: francescoK@uhrc.edu

Received: 21-Oct-2024, Manuscript No. AJPBP-24-153908 ; Editor assigned: 23-Oct-2024, Pre QC No. AJPBP-24-153908 (PQ); Reviewed: 07-Nov-2024, QC No. AJPBP-24-153908 (PQ); Revised: 15-Nov-2024, Manuscript No. AJPBP-24-153908 (R); Published: 22-Nov-2024

Description

Enzymes play a pivotal role in the physiological processes of the body, acting as biological catalysts that regulate biochemical reactions. In the context of neurodegenerative diseases, enzymes are often implicated in the mechanisms underlying cell dysfunction, degeneration, and death. These diseases, which include Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Huntington’s Disease (HD), and Amyotrophic Lateral Sclerosis (ALS), are characterized by the progressive loss of neuronal function and structure

Enzymes in neurodegenerative diseases

Neurodegenerative diseases are associated with a variety of enzyme dysfunctions, including abnormal enzyme activation, altered substrate metabolism, and enzyme inhibition, all of which contribute to the accumulation of toxic metabolites or the dysfunction of cellular processes that are significant for neuronal survival. These pathological changes can affect several pathways, such as protein folding and aggregation, oxidative stress, inflammation, and apoptosis, all of which are linked to enzyme activity.

Proteolytic enzymes and protein misfolding

In neurodegenerative diseases, proteolytic enzymes are involved in the degradation of misfolded proteins that accumulate in neurons. For instance, in Alzheimer’s disease, the accumulation of amyloid- beta plaques is a hallmark. Amyloid Precursor Protein (APP) is processed by secretases, a group of enzymes including beta-secretase and gamma- secretase, which produce amyloid-beta peptides. In healthy brains, these peptides are cleared, but in AD, the accumulation of these peptides contributes to neurotoxicity.

Similarly, in Parkinson’s disease, the accumulation of alpha-syncline in Lewy bodies is thought to be a result of defective proteolysis. The enzyme responsible for the degradation of alpha-syncline, such as the Ubiquitin-Proteasome System (UPS), becomes impaired in Parkinson’s disease (PD). The failure of these proteolytic enzymes to remove aggregated proteins leads to cellular dysfunction, oxidative stress, and ultimately neurodegeneration

Oxidative stress and enzyme dysfunction

Oxidative stress plays a significant role in the pathogenesis of neurodegenerative diseases, and several enzymes are involved in the generation and elimination of Reactive Oxygen Species (ROS). In diseases like Parkinson’s, mitochondrial dysfunction leads to the increased production of ROS, which causes oxidative damage to proteins, lipids, and DNA. Enzymes such as Super-Oxide Dismutase (SOD) and catalase are responsible for detoxifying ROS, but mutations or dysfunction of these enzymes contribute to increased oxidative stress and neuronal death. In ALS, the SOD1 gene is implicated, and mutations in SOD1 lead to the production of toxic free radicals, contributing to motor neuron degeneration.

In Alzheimer’s disease, oxidative stress is exacerbated by the presence of amyloid-beta plaques, which can interact with metal ions like copper and iron, generating ROS. Enzymes that regulate metal homeostasis, such as metallothioneins, can also be disrupted in neurodegenerative diseases, exacerbating oxidative damage.

Inflammatory enzymes and neuroinflammation

Neuroinflammation, characterized by the activation of glial cells and the release of pro- inflammatory cytokines, is a common feature of many neurodegenerative diseases. Enzymes like Cyclooxygenase (COX), which are involved in the synthesis of prostaglandins, and inducible

In Alzheimer’s disease, for example, activated microglia produce inflammatory cytokines and enzymes such as COX-2, which exacerbate neuronal damage. Similarly, in PD, neuroinflammation is mediated by the activation of the NLRP3 inflammasome, leading to the production of pro- inflammatory cytokines, which can further damage dopaminergic neurons.

Enzymes in cell death pathways

Enzymes also play a important role in regulating apoptotic and necrotic cell death pathways, which are central to the loss of neurons in neurodegenerative diseases. Caspases, a family of cysteine proteases, are key mediators of apoptosis. In Alzheimer’s disease, caspases are activated in response to amyloid-beta accumulation, triggering programmed cell death in neurons. In Parkinson’s disease, caspase activation is similarly involved in dopaminergic cell death following oxidative stress and mitochondrial dysfunction.

Targeting enzymes for therapeutic intervention

Given the central role of enzymes in neurodegenerative diseases, targeting enzyme activity has become an area of intense research for potential therapies. For example, inhibitors of beta-secretase and gamma- secretase are being developed to reduce amyloid- beta production in Alzheimer’s disease. Similarly, enzyme inhibitors that target proteases involved in neuroinflammation, such as COX inhibitors, are being explored as potential treatments for Parkinson’s and Alzheimer’s diseases.

In addition, the development of Enzyme Replacement Therapies (ERT) is a promising approach for treating neurodegenerative disorders caused by specific enzyme deficiencies, such as in lysosomal storage diseases.

Conclusion

Enzymes are fundamental to the normal functioning of the brain, but their dysfunction is intricately linked to the progression of neurodegenerative diseases. Abnormal proteolysis, oxidative stress, inflammation, and altered apoptotic pathways all contribute to neuronal damage and death, underscoring the importance of enzymes in these diseases. Understanding the role of enzymes in disease mechanisms opens the door to novel therapeutic strategies aimed at modulating enzyme activity to slow down or halt neurodegeneration. Research into enzyme-targeted treatments offers hope for improving the quality of life for individuals affected by these debilitating conditions.

Copyright: @ 2024 The Authors. This is an open access article under the terms of the Creative Commons Attribution Non Commercial Share Alike 4.0 (https://creativecommons.org/licenses/by-nc-sa/4.0/) This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.