Introduction to Enzymes in Neurodegeneration

Neurodegenerative diseases are a group of disorders characterized by progressive degeneration of the nervous system, leading to a decline in cognitive function, movement control, or both. This chapter elucidates the essential role of enzymes in the development of neurodegenerative diseases (NDDs), particularly Alzheimer’s disease (AD), focusing on enzymes such as neprilysin (NEP), endothelin-converting enzyme (ECE), insulin-degrading enzyme (IDE), and plasmin, emphasizing their roles in amyloid-beta (Aβ) metabolism and therapeutic strategy development. Reduced levels of NEP and ECE in AD patients lead to pathological Aβ accumulation, suggesting that upregulating these enzymes could alleviate AD symptoms by promoting Aβ clearance. IDE, which degrades both insulin and Aβ, is examined in the context of its role in insulin resistance and AD pathology, suggesting therapeutic benefits from upregulating IDE activity. Plasmin, a protease involved in Aβ fibril degradation, shows reduced activity in AD, highlighting the need for interventions to enhance its function. This chapter also discusses the impact of polyglutamylating enzymes on microtubule dynamics and neuronal stability, identifying their dysfunction as a contributor to neuronal damage, and advocating a potential therapeutic target. Furthermore, the renin-angiotensin system (RAS), specifically the enzymes angiotensin-converting enzyme (ACE) and ACE2, is discussed in relation to neuroinflammation and NDDs, with evidence suggesting that ACE inhibitors and angiotensin receptor blockers might provide neuroprotective effects. The importance of lifestyle factors such as diet and physical activity in managing NDDs is also emphasized. This comprehensive examination of enzymatic roles and lifestyle impacts lays the groundwork for developing multifaceted strategies to combat neurodegeneration.