GENE regulation in
DISEASE
M icroscopic analysis of postmortem brain tissue from individuals with Alzheimer’s disease reveals many changes thought to contribute to cellular damage to the brain. The current belief in the field is that Alzheimer’s disease-related brain changes result from a complex interplay between ab- normal tau and beta-amyloid proteins, along with other yet-to-be-discovered factors. Beta-amyloid proteins clump together and form plaques that collect between neurons, while neurofibrillary tangles are abnormal accumulations of tau protein that build up inside neurons. Both abnor- malities disrupt cell function, causing cell damage and cell death. The progressive build-up of beta-amyloid and tau protein begins long before individuals show their first symptoms of the disease. While increased levels of beta-amyloid and tau pro- teins are implicated in the pathology and devastation of Alzheimer’s disease, less is known about how and why the proteins accumulate and function incorrectly in the first place. In rare cases, a single gene mutation directly caus- es Alzheimer’s disease through the beta-amyloid pathway. These include single-gene variants in amyloid precursor protein ( APP ), Presenilin 1 and 2 ( PSEN1/2 ). However, for most common cases of Alzheimer’s, genetic contributors come in the form of non-determinant risk, such as through a form of apolipoprotein E ( APOE ∑ 4 ), which is less directly linked to the key pathologies of the disease. Changes in the genetic code are not the only way a gene’s function can be altered. Gene expression is
controlled by transcription factors and other transcription- al elements that cause genes to be expressed more or less than needed. Certain non-coding regions of DNA can also regulate gene expression. Promoters, located close to the transcription start site, provide binding sites for transcrip- tion factors. Enhancers are located further from the start site and provide binding sites for other proteins that help activate transcription. Changes in the function of promot- ers and enhancers can affect gene expression. A prominent theory in the neurodegenerative disease field is that toxic levels of accumulation of beta-amyloid and tau proteins in neurons can lead to disease. Hudson- Alpha faculty investigator Nick Cochran, PhD , and his lab investigate gene regulation processes involved in Alzhei- mer’s disease development and function as one possible cont. on p. 24
The burden of aLZHEIMER’S DISEASE IS PREDICTED TO DOUBLE EVERY 20 YEARS, REACHING 139 MILLION PEOPLE BY YEAR 2050
HUDSONALPHA INSTITUTE FOR BIOTECHNOLOGY
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