SCICONX Journal of Biomedical Science

Neurodegenerative Disease Models: Insights from Biomedical Research

Author(s) info »

Abstract

Neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and Amyotrophic Lateral Sclerosis (ALS), represent a major global health challenge. Characterized by progressive loss of neurons and neurological function, these disorders lead to cognitive decline, motor dysfunction, and ultimately severe disability. Despite significant research, effective therapies remain limited, primarily due to the complex etiology and heterogeneous nature of neurodegeneration. Biomedical research has focused on developing experimental models to understand the molecular mechanisms underlying neurodegenerative diseases and to evaluate potential therapeutic strategies. Disease models, ranging from in vitro cellular systems to in vivo animal models, have provided critical insights into pathological pathways such as protein misfolding, oxidative stress, mitochondrial dysfunction, and neuroinflammation. This article explores the current neurodegenerative disease models, their contributions to biomedical research, advantages, limitations, and future perspectives.

Neurons, Excitotoxicity, Oxidative stress, Alzheimer’s

DESCRIPTION

Neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and Amyotrophic Lateral Sclerosis (ALS), represent a major global health challenge. Characterized by progressive loss of neurons and neurological function, these disorders lead to cognitive decline, motor dysfunction, and ultimately severe disability. Despite significant research, effective therapies remain limited, primarily due to the complex etiology and heterogeneous nature of neurodegeneration. Biomedical research has focused on developing experimental models to understand the molecular mechanisms underlying neurodegenerative diseases and to evaluate potential therapeutic strategies. Disease models, ranging from in vitro cellular systems to in vivo animal models, have provided critical insights into pathological pathways such as protein misfolding, oxidative stress, mitochondrial dysfunction, and neuroinflammation. This article explores the current neurodegenerative disease models, their contributions to biomedical research, advantages, limitations, and future perspectives.

Cellular models of neurodegeneration

Cellular models serve as foundational tools for studying disease mechanisms at a molecular and biochemical level.

Primary neuronal cultures: Derived from embryonic or postnatal rodent brains, these cultures maintain many neuronal characteristics, including synaptic connections and electrophysiological properties. Applications include studying neuronal toxicity, excitotoxicity, oxidative stress, and protein aggregation. Limited lifespan, variability between preparations, and ethical considerations.

Immortalized cell lines: Human neuroblastoma cell lines (e.g., SH-SY5Y) are widely used for modeling neurodegeneration. Advantages are easy maintenance, high reproducibility, and suitability for high-throughput screening. Disadvantages are may lack full neuronal characteristics and synaptic complexity.

Induced Pluripotent Stem Cell (iPSC)-derived neurons: Patient-derived iPSCs allow the generation of disease-relevant neurons carrying patient-specific genetic mutations. Provide personalized insights into disease mechanisms and enable drug screening in a human cellular context. iPSC models have been used to study Alzheimer’s (APP, PSEN mutations) and Parkinson’s disease (LRRK2, SNCA mutations). Limitations differentiation protocols are time-consuming, and cells may not fully mature in vitro.

3D Organoids: Brain organoids mimic tissue architecture, neuronal networks, and microenvironment. Used to study complex phenomena such as synaptic connectivity, protein aggregation, and neuroinflammation. Provide more physiologically relevant models compared to 2D cultures. Challenges variability in organoid size and composition, and lack of vascularization.

Molecular mechanisms explored using disease models

Neurodegenerative disease models have helped elucidate several key pathological mechanisms:

Protein misfolding and aggregation: Models have demonstrated the accumulation of amyloid-β plaques in Alzheimer’s disease and α-synuclein Lewy bodies in Parkinson’s disease. Cellular and animal models help screen compounds that reduce protein aggregation or enhance clearance via autophagy.

Oxidative stress and mitochondrial dysfunction: Oxidative damage contributes to neuronal loss in multiple diseases.

Models allow the study of reactive oxygen species generation, mitochondrial respiration deficits, and therapeutic antioxidants.

Neuroinflammation: Microglia and astrocyte activation contribute to neuronal damage. Models help evaluate anti inflammatory interventions and understand the role of immune responses in neurodegeneration.

Synaptic dysfunction and neurotransmitter imbalance: Loss of synaptic connectivity precedes neuronal death. Models allow detailed analysis of glutamatergic, dopaminergic, and cholinergic signaling, guiding therapy development.

Applications in drug discovery and therapeutics

Neurodegenerative disease models are essential for translational biomedical research high-throughput drug screening iPSC derived neurons and immortalized cell lines allow rapid testing of therapeutic compounds. Target validation genetic models help identify and validate disease-associated pathways. Preclinical efficacy testing: Rodent and primate models are used to assess behavioral outcomes and pharmacokinetics. Gene and cell therapy evaluation: Transgenic and humanized models provide proof-of-concept for advanced therapies. Models have directly contributed to the development of FDA-approved drugs such as donepezil and rivastigmine for Alzheimer’s, and levodopa and dopamine agonists for Parkinson’s disease.

Limitations and future directions

While neurodegenerative disease models have provided significant insights, they have limitations:

Incomplete recapitulation of human disease: No model fully mimics all aspects of human neurodegeneration.

Species differences: Rodent and invertebrate models may not accurately reflect human brain complexity.

Time and cost constraints: Especially in non-human primates or long-lived rodent models.

Genetic heterogeneity: Human patients exhibit diverse genetic backgrounds, challenging model generalizability. Future directions in biomedical research include Integration of multi omics approaches (genomics, proteomics, metabolomics) to understand disease pathways. Advanced iPSC and organoid technologies to develop patient-specific models. CRISPR-based genome editing to create more precise disease models. Artificial intelligence and machine learning to predict disease progression and therapeutic responses. Humanized animal models to better recapitulate human pathophysiology. These innovations promise to enhance model fidelity and improve the translational relevance of preclinical research. Neurodegenerative disease models are indispensable tools in biomedical research, providing critical insights into disease mechanisms, therapeutic targets, and drug discovery. Cellular models, including primary neurons, iPSC derived neurons, and organoids, allow mechanistic studies at the molecular level. Animal models, ranging from rodents to non human primates, enable in vivo evaluation of disease progression and therapeutic interventions. While no model fully replicates human neurodegenerative disease, ongoing innovations such as patient-specific iPSC models, organoids, and multi omics integration are bridging the gap between experimental research and clinical applications. Continued development and refinement of these models will be pivotal in understanding neurodegeneration and in the discovery of effective therapies, ultimately improving patient outcomes and quality of life.

Author(s) Info

Received date: 20-Sep-2025, Manuscript No. JBS-25-165669; Editor Assigned: 23-Sep-2025, Pre QC No. JBS-25-165669 (PQ); Reviewed: 07-Oct-2025, QC No. JBS-25-165669; Revised: 14-Oct-2025, Manuscript No. JBS-25-165669 (R); Published date: 21-Oct-2025