A study has uncovered a biological process in which thyroid hormones and proteins in the liver work together to regulate cholesterol, an imbalance of which is considered common in neurodegenerative diseases.
Researchers said the “previously unrecognised” process could be targeted to prevent one from developing ageing-related disorders, such as Alzheimer’s and Parkinson’s diseases.
The study, led by the University of Houston in the US, reviewed previously published research on how thyroid hormones and liver proteins (liver X receptors) function, and found that the two were part of a single process by which the endocrine system balances cholesterol in the brain.
Further, a decline in the function of liver proteins crucial to regulating thyroid in the brain was found to lead to ageing-related degeneration in neurons (neurodegeneration).
Therefore, the “discovery could fundamentally change how we approach treatment for various neurodegenerative conditions”, said lead author Margaret Warner, a professor at the department of biology and biochemistry, University of Houston.
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“A review of the literature clearly shows that these two receptors work together to regulate cholesterol homeostasis and dysregulation of cholesterol homeostasis is a common factor in neurodegenerative diseases,” the authors wrote in the study published in the journal Genomic Psychiatry.
Alzheimer’s disease treatments aimed at activating liver proteins known to regulate cholesterol and lipid (fat) metabolism could help reduce amyloid plaque formation and improve memory, the researchers proposed.
Amyloid plaques are clumps of amyloid proteins in the brain which are considered a hallmark of Alzheimer’s disease and are a common target for developing drugs.
The authors said their review revealed a higher prevalence of hypothyroidism — in which thyroid is produced in insufficient levels — in Alzheimer’s disease, but cautioned that they could not discern if it was a risk factor for or a consequence of the neurodegenerative condition.
The team also proposed looking at processes involving liver X receptors for treating Parkinson’s disease because of their protective effect on dopamine-producing neurons. A lack of the brain chemical dopamine is considered to play a key role in causing Parkinson’s disease.
The process involving thyroid and liver proteins could also be targeted for treating amyotrophic lateral sclerosis, a progressive disease affecting movement neurons in the brain and spinal cord, and multiple sclerosis, which is an autoimmune condition, the authors suggested.
“What’s particularly intriguing is the age-dependent nature of these protective effects. Understanding why certain neurons become vulnerable to degeneration as we age could be key to developing preventive treatments,” said co-author Xiaoyu Song from the University of Houston.
