Epigenetics Implications for Treating Neurodegenerative Diseases

Neurodegenerative diseases are defined as the loss of neurons from specific regions of the central nervous system (CNS). Recently, research has focused on identifying mechanisms that lead to neurodegeneration, while therapeutic approaches have been primarily targeted to prevent neuronal loss. Neurodegenerative diseases refer to a range of neuronal disabilities accompanied by massive neuronal loss at the late stages of the diseases. The implication of epigenetic changes associated with two representative neurodegenerative diseases and possible application of pharmaceutical modulation of these epigenetics changes as a disease treatment.

These neurodegenerative diseases include Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and Lou Gehrig’s disease/Amyotrophic lateral sclerosis (ALS).

The recent advance in the related techniques such as NGS and mass spectrometry we are now able to recognize some of key mediators and roughly figure out the working mechanisms of these epigenetic changes. However, epigenetic deregulations is not only specifically limited to two neurodegenerative diseases.

Neurodegenerative Disorders

Alzheimer's disease: It also referred to simply as Alzheimer's, is a chronic neurodegenerative disease that usually starts slowly and worsens over time. It is the cause of 60–70% of cases of dementia. About 70% of the risk is believed to be genetic with many genes usually involved. Other risk factors include a history of head injuries, depression, or hypertension. The disease process is associated with plaques and tangles in the brain.

Parkinson’s disease: Amongst all neurodegenerative disorders, the Parkinson’s disease is the second most common after Alzheimer’s. In Parkinson’s disease, a correlation between neurodegeneration and epigenetics has not been extensively exploited so far. However, several genes common to both Parkinson’s and Cancer carry an abnormal methylation pattern in the latter, indicating a possible shared similarity in the former.

Huntington’s disease: Huntington's disease is an inherited disease that causes the progressive breakdown (degeneration) of nerve cells in the brain. Huntington's disease has a broad impact on a person's functional abilities and usually results in movement, thinking and psychiatric disorders. Likewise, a growing body of evidence proposes epigenetic mechanisms to be of prime importance in the Huntington’s disease. DNA methylation is believed to be the key factor responsible for reduced expression of the gene ADORA2A, encoding adenosine receptor protein, via enhanced methylation Thus, ADOR2A protein is being considered as a potential therapeutic target in Huntington’s disorder.