A US patent has recently been granted to P. Hemachandra Reddy, Ph.D. and Subodh Kumar, Ph.D. Department of Internal Medicine, Texas Tech University Health Sciences Center College of Medicine. The patent “MicroRNA-455-3p as a peripheral biomarker for Alzheimer’s disease” focuses on developing a novel blood-based biomarker for early detection of Alzheimer’s disease.
The present invention includes a novel method for identifying an Alzheimer’s patient prior to reaching clinical disease classification and is based on the increased levels of microRNA-455-3p in a blood, serum, or plasma sample obtained from an Alzheimer’s disease patient with cognitive impairment compared to a healthy control subject. With no clinical evidence of Alzheimer’s disease.
As people get older, a gradual loss of cognitive function often indicates the onset of Alzheimer’s disease or similar types of dementia. These conditions cause a person to lose some of their intellectual functions such as the ability to think about ideas, retain memories, and apply thinking skills.
The prevalence of these chronic, age-related conditions is increasing each year, and recent studies have shown that they disproportionately affect the elderly population of rural West Texas. Research also indicates that minority communities in rural West Texas often experience the highest rate of Alzheimer’s disease or other forms of dementia due to a lack of health services and poor access to appropriate health care services.
The patented biomarker technology is based on a small, single-stranded, non-coding RNA molecule, called a microRNA (miRNA), that helps cells control the types and amounts of proteins they make. MicroRNA-455-3p, also known as miR-455-3p, is a member of the widely conserved miRNA family located on human chromosome 9.
The role of miR-455 is implicated in many normal physiological processes and diseases such as cartilage development, lipogenesis and preeclampsia, Reddy said. “It is also implicated in various types of cancer such as colon cancer, prostate cancer, hepatocellular carcinoma, kidney cancer, oral squamous cell carcinoma, melanoma and non-small cell lung cancer,” Reddy added.
Reddy’s lab discovered the biomarker miR-455-3p and its therapeutic significance by performing a global microarray analysis of serum samples from three groups: Alzheimer’s patients; Individuals with moderate cognitive decline. and healthy patients who do not know the signs of disease.
“Our findings revealed significantly higher levels of miR-455-3p in Alzheimer’s patients than in individuals with mild cognitive impairment and healthy patients,” Reddy explained. Furthermore, validation analysis using different types of Alzheimer’s samples such as serum, postmortem brains, fibroblasts, B lymphocytes, Alzheimer’s cell lines, mouse models of Alzheimer’s disease, and CSF cells from Alzheimer’s patients confirmed the potential of the markers. The biosynthesis of miR-455 -3 p.
Reddy’s group believes that miR-455-3p may act as a key biomarker because it is part of the mechanism that leads to Alzheimer’s disease, namely that it modulates amyloid-beta (AMB) and amyloid-beta levels. Amyloid-peptides consist of 36-43 amino acids, which are the primary component of the amyloid plaques found in the brains of Alzheimer’s patients. To confirm that the amyloid-beta precursor protein (AβPP) is the target of miR-455-3p, Reddy and colleagues used the luciferase reporter assay, which is an assay used to determine whether the protein has the ability to activate or repress the protein. Expression of the target gene. Moreover, mouse neuroblastoma was used to establish a protective role of miR-455-3p against amyloid-beta-induced toxicity. Results obtained by Reddy and colleagues suggested that miR-455-3p enhances cell survival and extends lifespan, and further suggested that elevated levels of miR-455-3p reduce Aβ toxicity, enhance mitochondrial biogenesis and synaptic activity, and maintain healthy mitochondrial dynamics.
The next transitional step was to understand the function of microRNA-455-3p in whole animals. To achieve this, Reddy’s lab generated both transgenic (TG) and knockout (KO) mouse models of miR-455-3p. They found that mice with overexpressed microRNA-455-3p lived five months longer than their wild-type counterparts, while depleted mice lived four months shorter than wild-type mice. The Morris water maze test, which tests rodent-specific learning, showed improvement in cognitive behavior, spatial learning, and memory in miR-455-3p mice that were overexpressed relative to age-matched wild-type mice.
“Overall, miR-455-3p overexpressed in mice showed protective effects, while miR-455-3p depleted showed deleterious effects in mice with respect to age, cognitive behavior, mitochondrial activities and synapses,” Reddy said. “Based on this evidence, we cautiously conclude that miR-455-3p is a promising peripheral biomarker and therapeutic candidate for Alzheimer’s disease.”
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