PhD student Matthew Durk and Professor K. Sandy Pang at the University of Toronto’s Leslie Dan Faculty of Pharmacy were lead and senior authors on a study recently published as a featured article in the Journal of Neuroscience (Vol 34:7091-7101, 2014).
This study explores the role the Vitamin D receptor may play in the prevention and treatment of Alzheimer’s disease.
Vitamin D has long been understood to play an important role in several bodily functions, including calcium homeostasis and bone growth. However, it’s role in immune function and cell proliferation are less known.
Vitamin D forms an active metabolite (1,25-dihydroxyvitamin D3) by the liver, then kidney, which works by binding with the vitamin D receptor to regulate gene transcription. In the brain, this interaction leads to the expression of proteins and genes that influence brain development.
Recent studies have shown that vitamin D deficiency during development may contribute to increased risk of several neurodevelopmental disorders, and that low vitamin D levels occur in people with some neurodegenerative disorders including Alzheimer’s disease.
Recognizing the possible link between vitamin D deficiency and neurological impairments, the Pang lab, in collaboration with Professor Paul Fraser (Tanz Centre for Research in Neurodegenerative Diseases) and Professor Jeff Henderson (Leslie Dan Faculty of Pharmacy), is exploring the role of the vitamin D receptor in contributing to, or preventing, these issues.
“Treatment with 1,25-dihydroxyvitamin D3 in animal models containing the human β-amyloid precursor protein,” notes Dr. K. Sandy Pang, “resulted in increased expression of P-glycoprotein – an important protein that pumps β-amyloid 40 and 42, peptides, considered to play key roles in Alzheimer’s disease, out of the brain– which helped to reduce insoluble (plaque) and solubleβ-amyloid levels and improve cognitive function.”
Based on this discovery, the study concludes that increasing P-glycoprotein by the vitamin D receptor has the ability to slow the progression of Alzheimer’s disease at early onset. As well, the project suggests that maintenance of adequate vitamin D levels in the elderly may be crucial in preventing neurodegeneration.
Source of text: University of Toronto – Pharmacy
Original research article: Durk MR, Han K, Chow EC, Ahrens R, Henderson JT, Fraser PE, Pang KS.
1α,25-Dihydroxyvitamin D3 Reduces Cerebral Amyloid-β Accumulation and Improves Cognition in Mouse Models of Alzheimer’s Disease. J Neurosci. 2014 May 21;34(21):7091-101. doi: 10.1523/JNEUROSCI.2711-13.2014.
