Biochemistry & Physiology: Open Access
Open Access

Neurodegenerative diseases (NDs) are a group of disorders that primarily affect the neurons of the central nervous system, leading to progressive degeneration and dysfunction. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most prevalent NDs, both associated with significant morbidity and mortality. The global aging population has led to a rise in the incidence of these diseases, making understanding their molecular basis a critical area of scientific inquiry. AD is characterized by the deposition of amyloid-beta plaques, tau protein tangles, and neuronal loss, resulting in cognitive decline. Conversely, PD is primarily associated with the loss of dopaminergic neurons in the substantia nigra, accompanied by the presence of Lewy bodies, abnormal protein aggregates that disrupt cellular function. Despite the clinical distinction between AD and PD, both diseases share common pathogenic mechanisms, including oxidative stress, neuroinflammation, mitochondrial dysfunction, and impaired protein homeostasis. These shared mechanisms may provide therapeutic opportunities that transcend individual disease boundaries [1].

The pathogenesis of AD is deeply linked to the abnormal processing of amyloid precursor protein (APP) and tau proteins, which form toxic aggregates in the brain, leading to synaptic loss and cognitive deficits. In PD, mutations in the LRRK2 and SNCA genes, along with the formation of Lewy bodies containing alpha-synuclein, contribute to dopaminergic cell death. Furthermore, a combination of genetic predisposition and environmental factors such as exposure to toxins or trauma can influence disease onset and progression. This review will focus on the molecular mechanisms that underlie the pathophysiology of AD and PD, examining how disruptions in protein folding, degradation, and neuronal signaling pathways contribute to disease. Understanding these molecular events will not only enhance our comprehension of disease pathogenesis but also facilitate the development of novel therapeutic strategies aimed at halting or reversing neurodegeneration [2].

Methods

To explore the molecular mechanisms underlying Alzheimer’s disease (AD) and Parkinson’s disease (PD), we conducted a comprehensive review of recent scientific literature. We analyzed studies that investigated the role of key molecular pathways, including oxidative stress, protein aggregation, neuroinflammation, and mitochondrial dysfunction. Research articles were selected based on their focus on genetic factors, such as mutations in the APP, PSEN1, PSEN2, and LRRK2 genes, and their relevance to the pathophysiology of AD and PD. Additionally, studies examining the impact of environmental factors, including toxins and trauma, were also reviewed [3]. Molecular and cellular studies involving in vitro models, animal models, and human tissue samples were included to understand the cellular mechanisms implicated in neuronal degeneration. Techniques such as immunohistochemistry, proteomics, RNA sequencing, and gene editing technologies were considered in evaluating the molecular changes associated with these diseases. A particular focus was placed on understanding how disruptions in protein homeostasis, autophagy, and synaptic function contribute to neurodegeneration. This methodological approach allowed for a holistic view of the molecular factors involved in AD and PD, facilitating the identification of potential therapeutic targets for future research [4].

Results

The molecular analysis of Alzheimer’s disease (AD) and Parkinson’s disease (PD) revealed several key pathogenic mechanisms shared by both conditions. In AD, the accumulation of amyloid-beta (Aβ) plaques and tau tangles were identified as central to the pathophysiology. The cleavage of amyloid precursor protein (APP) by secretases results in the generation of Aβ peptides, which aggregate to form plaques. These plaques disrupt synaptic function, trigger inflammation, and activate neurotoxic pathways that lead to neuronal death.

Hyperphosphorylation of tau protein further exacerbates the pathological process by promoting the formation of neurofibrillary tangles, which impair axonal transport and disrupt neuronal communication. In PD, mutations in the LRRK2 and SNCA genes were shown to contribute to the accumulation of alpha-synuclein, forming Lewy bodies that disrupt cellular function [5]. The loss of dopaminergic neurons in the substantia nigra was accompanied by oxidative stress, mitochondrial dysfunction, and impaired protein degradation mechanisms. Additionally, neuroinflammation was found to exacerbate neuronal damage, with activated microglia and astrocytes playing a central role in the progression of both diseases.

Studies also highlighted the role of autophagy and the ubiquitin-proteasome system in maintaining cellular homeostasis. Dysfunction in these pathways leads to the accumulation of misfolded proteins and organelle damage, further contributing to neurodegeneration. Together, these results provide insights into the molecular events that drive the pathophysiology of AD and PD and point to potential therapeutic targets for future interventions [6].

Discussion

The results of this review underscore the complexity and overlap of molecular mechanisms in Alzheimer’s disease (AD) and Parkinson’s disease (PD). While each disease has its distinct pathological features, such as amyloid plaques in AD and alpha-synuclein aggregates in PD, both conditions share common underlying processes, including oxidative stress, mitochondrial dysfunction, and neuroinflammation. These findings suggest that therapeutic strategies targeting these shared pathways could offer broader benefits for both diseases, particularly in the context of early-stage intervention [7].

Oxidative stress and mitochondrial dysfunction are critical contributors to neuronal damage in both AD and PD. Mitochondria are essential for maintaining cellular energy homeostasis, and their dysfunction leads to the accumulation of reactive oxygen species (ROS), which further damage proteins, lipids, and DNA. The inability to clear misfolded proteins, such as amyloid-beta and alpha-synuclein, exacerbates this oxidative damage and disrupts neuronal function [8].

Neuroinflammation, particularly the activation of microglia, has been identified as a significant factor in both AD and PD. Microglial activation releases pro-inflammatory cytokines that further promote neuronal injury. The failure of neuroprotective mechanisms, such as autophagy and the ubiquitin-proteasome system, exacerbates protein aggregation and cellular dysfunction.

Moreover, the discovery of genetic mutations associated with AD (APP, PSEN1, PSEN2) and PD (LRRK2, SNCA) has provided valuable insights into disease mechanisms. These mutations contribute to the accumulation of toxic proteins, highlighting the potential for genetic-based therapies. Future research focusing on gene editing, protein aggregation inhibitors, and neuroinflammation modulators may lead to the development of disease-modifying therapies [9,10].

Conclusion

In conclusion, the molecular basis of Alzheimer’s disease (AD) and Parkinson’s disease (PD) involves complex interactions between genetic factors, protein misfolding, oxidative stress, neuroinflammation, and mitochondrial dysfunction. Both diseases share common pathogenic mechanisms, such as the accumulation of toxic proteins (amyloid-beta in AD and alpha-synuclein in PD), oxidative damage, and impaired protein homeostasis. These molecular insights not only deepen our understanding of disease pathophysiology but also highlight potential therapeutic targets. For instance, targeting oxidative stress, modulating neuroinflammation, and enhancing protein clearance mechanisms offer promising strategies for intervention. Moreover, genetic discoveries have paved the way for precision medicine approaches, where therapies can be tailored to specific genetic profiles, offering hope for more effective treatments. While current treatments primarily address symptoms, the future of neurodegenerative disease therapy lies in disease-modifying interventions that can halt or reverse neurodegeneration. Continued research is essential to uncover the precise mechanisms of AD and PD, ultimately leading to better diagnostic tools and targeted therapies for these devastating conditions.

Acknowledgement

None

Conflict of Interest

None

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