Genomic Approaches to Understanding the Pathogenesis of Neurodegenerative Diseases

Cardos Garry^*
*Correspondence: Cardos Garry, Department of Molecular Science, North Park University, Chicago, USA, Email:

Keywords

Neurodegenerative diseases • Nervous system • DNA sequence • Genomics

Introduction

Neurodegenerative Diseases (NDs) are a group of chronic and progressive disorders that affect the nervous system, causing progressive and irreversible deterioration of brain function. These diseases include Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Huntington’s Disease (HD) and Amyotrophic Lateral Sclerosis (ALS), among others. NDs are characterized by the accumulation of abnormal proteins in the brain, the loss of neurons and the dysfunction of glial cells. Despite extensive research efforts, the etiology and pathogenesis of NDs remain poorly understood. However, genomic approaches have provided valuable insights into the mechanisms underlying NDs [1].

One promising approach is the use of gene therapy to target specific genes and pathways involved in NDs. For example, in AD, gene therapy approaches have been developed to target the production of amyloid beta or to increase the clearance of amyloid beta from the brain. In PD, gene therapy approaches have been developed to increase the production of dopamine or to reduce the production of alpha-synuclein. Genomic approaches have provided valuable insights into the mechanisms underlying NDs. GWAS have identified genetic variants that are associated with an increased risk of NDs, while transcriptomics and epigenetics have identified changes in gene expression patterns and epigenetic modifications that contribute to the development of NDs. Functional genomics studies have identified several genes and pathways that are involved in NDs, providing potential targets for the development of novel therapeutic approaches [2].

Neurodegenerative diseases are a group of disorders that result in progressive loss of function and structure of neurons in the brain and spinal cord. Some common examples of neurodegenerative diseases include Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic Lateral Sclerosis (ALS). The exact causes of neurodegenerative diseases are not fully understood, but several factors are believed to play a role in their pathogenesis.

These factors include genetic, environmental and lifestyle factors. Genetic factors are thought to be responsible for some neurodegenerative diseases, such as Huntington's disease, which is caused by a mutation in the HTT gene. Similarly, mutations in genes such as APP, PSEN1 and PSEN2 are known to contribute to the development of Alzheimer's disease. Environmental factors such as exposure to toxins, infections and head injuries can also lead to the development of neurodegenerative diseases. For example, Parkinson's disease is associated with exposure to pesticides and head injuries [3].

Lifestyle factors such as diet, physical activity and sleep patterns may also contribute to the development of neurodegenerative diseases. Chronic inflammation caused by an unhealthy diet and sedentary lifestyle has been linked to the development of Alzheimer's disease and Parkinson's disease. In summary, neurodegenerative diseases are complex disorders that result from a combination of genetic, environmental and lifestyle factors. Understanding the underlying mechanisms that lead to the loss of neurons is crucial for developing effective treatments and preventative strategies. Genome-Wide Association Studies (GWAS) have been used to identify genetic variants that are associated with an increased risk of NDs. These studies involve the analysis of the entire genome of large cohorts of individuals with and without NDs, in order to identify genetic markers that are more frequent in the affected group. GWAS have identified several genetic variants that are associated with an increased risk of NDs, including the APOE ε4 allele, which is a major risk factor for AD and the SNCA gene, which is associated with PD [4].

Description

The pathogenesis of neurodegenerative diseases involves various cellular and molecular mechanisms that contribute to the progressive loss of neurons in the brain and spinal cord. Some of the key mechanisms include:

Protein misfolding and aggregation: In many neurodegenerative diseases, certain proteins within the neurons misfold and form aggregates or clumps that disrupt cellular function and cause cell death. For example, in Alzheimer's disease, the protein beta-amyloid accumulates in the brain, while in Parkinson's disease, the protein alpha-synuclein forms aggregates called lewy bodies.

Oxidative stress: Reactive Oxygen Species (ROS) are generated during normal cellular metabolism, but when their levels exceed the capacity of cellular defense mechanisms, they can damage cellular components such as DNA, lipids and proteins. ROS induced oxidative stress is believed to contribute to neuronal damage in neurodegenerative diseases.

Inflammation: Chronic inflammation in the brain can contribute to the progression of neurodegenerative diseases. Microglial cells, the immune cells of the brain, play a key role in the inflammatory response in neurodegenerative diseases, releasing pro-inflammatory cytokines that contribute to neuronal damage.

Mitochondrial dysfunction: Mitochondria are the energy-producing organelles in cells and mitochondrial dysfunction can lead to the generation of ROS and oxidative stress, as well as decreased energy production. Mitochondrial dysfunction is believed to contribute to the pathogenesis of several neurodegenerative diseases.

Excitotoxicity: Excessive stimulation of neurons by the neurotransmitter glutamate can cause cell death through a process called excitotoxicity. This process is believed to contribute to the death of neurons in neurodegenerative diseases such as ALS.

Transcriptomics involves the analysis of gene expression in different tissues, including the brain. Transcriptomic studies have identified changes in gene expression patterns that are associated with NDs. For example, in AD, there is a down regulation of genes that are involved in synaptic function and up regulation of genes involved in immune response and inflammation. In PD, there is a down regulation of genes involved in dopamine synthesis and up regulation of genes involved in oxidative stress and inflammation. Epigenetics involves the study of modifications to DNA that do not involve changes to the underlying DNA sequence. Epigenetic modifications can affect gene expression and contribute to the development of NDs. For example, in AD, there is a global increase in DNA methylation, which is associated with the down regulation of genes involved in synaptic function. In PD, there is a decrease in histone acetylation, which is associated with the down regulation of genes involved in dopamine synthesis. Functional genomics involves the analysis of the function of genes and their products. Functional genomics studies have identified several genes and pathways that are involved in NDs. For example, in AD, the Amyloid Precursor Protein (APP) and presently genes are involved in the production of amyloid beta, which is a major component of amyloid plaques. In PD, the SNCA gene is involved in the production of alpha-synuclein, which is a major component of Lewy bodies [5].

Conclusion

However, more research is needed to fully understand the complex interplay between genetic and environmental factors in the development of NDs. In conclusion, genomic approaches have provided valuable insights into the pathogenesis of NDs and have identified potential targets for the development of novel therapeutic approaches. However, more research is needed to fully understand the underlying mechanisms and to develop effective treatments for these devastating diseases.

Acknowledgement

None.

Conflict of Interest

None.

References

1. Hu, Liya, Sue E. Crawford, Joseph M. Hyser and Mary K. Estes, et al. "Rotavirus non-structural proteins: Structure and function." Curr Opin Virol 2 (2012): 380-388.

Google Scholar, Crossref, Indexed at

2. Desselberger, Ulrich. "Rotaviruses." Virus Res 190 (2014): 75-96.

Google Scholar, Crossref, Indexed at

3. Matthijnssens, Jelle, Christiaan A. Potgieter, Max Ciarlet and Viviana Parreno, et al. "Are human rotavirus strains the result of interspecies transmissions from sheep or other ungulates that belong to the mammalian order artiodactyla?." J Virol 83 (2009): 2917-2929.

Google Scholar, Crossref, Indexed at

4. Sinclair, Julie R. "Importance of a one health approach in advancing global health security and the sustainable development goals." Rev sci tech 38 (2019): 145-154.

Google Scholar, Crossref, Indexed at

5. Larsson, Anders. "AliView: A fast and lightweight alignment viewer and editor for large datasets." Bioinformatics 30 (2014): 3276-3278.

Google Scholar, Crossref, Indexed at