Epigenetics of neurodegenerative diseases

Parasagittal MRI of human head in patient with benign familial macrocephaly prior to brain injury (ANIMATED)

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Brain-derived neurotrophic factor - PDB id 1BND

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Epigenetics of neurodegenerative diseases

The study of the epigenetics of neurodegenerative diseases focuses on how epigenetic mechanisms contribute to the development and progression of diseases that affect the nervous system. These diseases include Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic lateral sclerosis (ALS), among others. Epigenetic changes can influence gene expression without altering the underlying DNA sequence, and they include mechanisms such as DNA methylation, histone modification, and non-coding RNAs.

Epigenetic Mechanisms

Epigenetic mechanisms play a crucial role in regulating gene expression in the nervous system. The primary mechanisms include:

• DNA methylation: The addition of a methyl group to the DNA molecule, typically at cytosine bases in CpG islands, which can repress gene transcription.
• Histone modification: The addition or removal of chemical groups to histone proteins, affecting how tightly DNA is wound around histones and thus regulating gene accessibility.
• Non-coding RNAs: RNA molecules that do not code for proteins but can regulate gene expression at the transcriptional and post-transcriptional levels.

Alzheimer's Disease

Alzheimer's disease (AD) is characterized by the accumulation of amyloid-beta plaques and neurofibrillary tangles in the brain. Epigenetic changes, such as altered DNA methylation and histone modifications, have been observed in genes associated with AD, including those involved in amyloid precursor protein (APP) processing and tau protein regulation.

Parkinson's Disease

Parkinson's disease (PD) is marked by the loss of dopaminergic neurons in the substantia nigra. Epigenetic alterations, such as changes in DNA methylation and histone acetylation, have been implicated in the regulation of genes involved in dopamine synthesis, mitochondrial function, and oxidative stress response.

Huntington's Disease

Huntington's disease (HD) is caused by a genetic mutation in the HTT gene, leading to the production of an abnormal huntingtin protein. Epigenetic modifications, including histone deacetylation and altered DNA methylation, have been shown to affect the expression of genes involved in neuronal survival and function.

Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons. Epigenetic changes, such as DNA methylation and histone modifications, have been observed in genes related to RNA processing, protein homeostasis, and neuroinflammation.

Research and Therapeutic Implications

Understanding the epigenetic mechanisms underlying neurodegenerative diseases can provide insights into disease pathogenesis and identify potential therapeutic targets. Epigenetic therapies, such as histone deacetylase inhibitors and DNA methyltransferase inhibitors, are being explored for their potential to modify disease progression.

See Also

• Epigenetics
• Neurodegenerative disease
• Alzheimer's disease
• Parkinson's disease
• Huntington's disease
• Amyotrophic lateral sclerosis

External Links

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