Neurodegenerative Diseases: Mechanisms, Challenges, and Emerging Biomedical approaches

Neurodegenerative diseases are a group of progressive disorders characterized by the  gradual loss of structure and function of neurons in the central nervous system. These  conditions, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and  amyotrophic lateral sclerosis (ALS), represent a growing global health burden due to ageing  populations and increased life expectancy. Understanding the biological mechanisms of underlying neurodegeneration is essential for developing effective therapeutic strategies  and improving patient outcomes. 

Overview of Neurodegenerative Diseases 

Neurodegenerative diseases primarily affect neurons, which are highly specialized and non regenerative cells responsible for transmitting information throughout the brain and spinal  cord. Unlike many other cells in the body, neurons have limited ability to repair or replace  themselves once damaged. As a result, neuronal degeneration leads to irreversible  functional decline, affecting memory, cognition, movement, and behaviour (Przedborski,  Vila and Jackson-Lewis, 2003). 

Alzheimer’s disease is the most common neurodegenerative disorder and is characterized  by progressive memory loss and cognitive impairment. Parkinson’s disease primarily  affects motor function, leading to tremors, rigidity, and bradykinesia. Huntington’s disease  is a genetic disorder associated with abnormal movements and cognitive decline, while ALS  leads to progressive muscle weakness due to motor neuron degeneration (Dugger and  Dickson, 2017). 

Pathophysiology and Molecular Mechanisms 

Several common molecular mechanisms contribute to neurodegeneration. One of the key  factors is protein misfolding and aggregation. In Alzheimer’s disease, accumulation of beta amyloid plaques and tau protein tangles disrupts neuronal communication and triggers cell  death. In Parkinson’s disease, alpha-synuclein aggregates form Lewy bodies, which impair  neuronal function (Ross and Poirier, 2004). 

Another important mechanism is oxidative stress. The brain consumes a large amount of  oxygen and is highly susceptible to damage caused by reactive oxygen species (ROS).  Excessive ROS production can damage DNA, proteins, and lipids, leading to neuronal  apoptosis. Mitochondrial dysfunction also plays a critical role, as impaired energy  production further increases oxidative stress and accelerates neuronal degeneration (Lin  and Beal, 2006).

Neuroinflammation is another significant contributor. Activation of microglia, the immune  cells of the central nervous system, results in chronic inflammation and release of pro inflammatory cytokines. While inflammation initially serves a protective function,  prolonged activation leads to neuronal damage and disease progression (Glass et al., 2010).

Biomedical Research and Diagnostic Advances 

Biomedical research has significantly improved the understanding of neurodegenerative  diseases. Advances in molecular biology, neuroimaging, and biomarker identification have  enabled earlier diagnosis and better disease monitoring. For instance, cerebrospinal fluid  (CSF) biomarkers such as beta-amyloid and tau proteins are used to detect Alzheimer’s  disease in its early stages. Neuroimaging techniques, including magnetic resonance imaging  (MRI) and positron emission tomography (PET), allow visualization of structural and  functional brain changes (Jack et al., 2018). 

Genetic research has also identified mutations associated with neurodegenerative diseases.  For example, mutations in the HTT gene cause Huntington’s disease, while mutations in  genes such as SNCA and LRRK2 are linked to Parkinson’s disease. Understanding these  genetic factors provides opportunities for targeted therapies and personalized medicine  approaches.

Emerging Therapeutic Approaches 

Despite extensive research, most neurodegenerative diseases currently have no cure.  Available treatments mainly focus on symptom management and slowing disease  progression. However, several emerging biomedical strategies show promise.

Stem cell therapy is being explored as a potential treatment to replace damaged neurons  and restore neural function. Stem cells have the ability to differentiate into various neuronal  types and may help repair neural circuits (Trounson and McDonald, 2015).

Gene therapy is another promising approach. Techniques such as CRISPR-Cas9 gene editing  may allow correction of disease-causing mutations. Additionally, gene therapy can be used  to deliver neuroprotective proteins that enhance neuronal survival.

Immunotherapy has gained attention in Alzheimer’s disease research. Monoclonal antibodies targeting beta-amyloid aim to reduce plaque accumulation and slow cognitive decline. 

Lifestyle and preventive strategies also play a role. Regular physical activity, a balanced diet,  cognitive stimulation, and management of cardiovascular risk factors have been associated  with reduced risk of neurodegenerative diseases (Livingston et al., 2020). 

Conclusion 

Neurodegenerative diseases represent a major challenge in modern biomedical science due  to their complex pathophysiology and lack of curative treatments. Advances in biomedical  research, including biomarker discovery, stem cell therapy, and gene editing technologies,  offer hope for improved diagnosis and treatment. 

References

Dugger, B.N. and Dickson, D.W. (2017) ‘Pathology of neurodegenerative diseases’, Cold  Spring Harbor Perspectives in Biology, 9(7), pp. 1–24.

Glass, C.K. et al. (2010) ‘Mechanisms underlying inflammation in neurodegeneration’, Cell,  140(6), pp. 918–934.

Jack, C.R. et al. (2018) ‘Toward a biological definition of Alzheimer’s disease’, Alzheimer’s &  Dementia, 14(4), pp. 535–562.

Lin, M.T. and Beal, M.F. (2006) ‘Mitochondrial dysfunction and oxidative stress’, Nature,  443(7113), pp. 787–795.

Livingston, G. et al. (2020) ‘Dementia prevention, intervention, and care’, The Lancet,  396(10248), pp. 413–446.

Przedborski, S., Vila, M. and Jackson-Lewis, V. (2003) ‘Neurodegeneration: What is it?’,  Journal of Clinical Investigation, 111(1), pp. 3–10.

Ross, C.A. and Poirier, M.A. (2004) ‘Protein aggregation and neurodegenerative disease’,  Nature Medicine, 10(7), pp. S10–S17.

Trounson, A. and McDonald, C. (2015) ‘Stem cell therapies in clinical trials’, Cell Stem Cell,  17(1), pp. 11–22.

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This article was prepared by Alisha Chantru (Brunel University).

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