Adult Neurogenesis in Neurodegenerative Diseases: Mechanisms of Dysregulation in Alzheimer’s and Parkinson’s Disease

TL;DR

This paper explores how adult neurogenesis is disrupted in Alzheimer’s and Parkinson’s diseases and discusses potential therapeutic strategies to restore it.

Contribution

The paper provides a comprehensive review of mechanisms linking impaired adult neurogenesis to Alzheimer’s and Parkinson’s diseases.

Findings

Impairments in adult neurogenesis are linked to chronic inflammation and oxidative stress in Alzheimer’s and Parkinson’s diseases.

Non-pharmacological interventions like diet and exercise may help modulate neurogenesis in neurodegenerative diseases.

A deeper understanding of neurogenesis regulation could lead to new therapies for slowing disease progression.

Abstract

Adult neurogenesis, the process of generating new, functional neurons in the mature central nervous system, represents a key mechanism of brain plasticity and a potential source of regeneration. This process occurs primarily within specialised neurogenic niches: the subgranular zone of the hippocampal dentate gyrus (SGZ) and the subependymal zone (SEZ). It is regulated by a complex network of endogenous factors (e.g., hormones, neurotrophins, growth factors) and exogenous factors (environment, stress, diet, physical activity). Impairments in neurogenesis are linked to the pathogenesis of neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). In their course, chronic inflammation, mitochondrial dysfunction, oxidative stress, and the accumulation of pathological proteins (β-amyloid, Tau protein, α-synuclein) create a microenvironment that inhibits the proliferation, differentiation, and survival of new neurons. This results in the exacerbation of cognitive and memory deficits. A review of the literature indicates that modulating neurogenesis through non-pharmacological interventions (e.g., a diet rich in anti-inflammatory compounds, physical exercise) and targeted therapeutic strategies represents a promising, albeit complex, research avenue. The primary challenge remains not only stimulating neuron generation but also ensuring their proper maturation, survival, and functional integration into existing neuronal circuits. A deeper understanding of the molecular and environmental mechanisms regulating adult neurogenesis may open new therapeutic possibilities for slowing the progression of neurodegenerative diseases.

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