N-chain protein glycosylation in the brain is an understudied aspect of glucose utilization that affects a variety of cellular processes, including resting membrane potential, axonal activation, and synaptic vesicle transport. In a recent study published in the journal Alzheimer's & DementiaIn entitled "Situ spatial glycomic imaging of mouse and human Alzheimer's disease brains", researchers from Kentucky reported that glucose utilization in the mouse and human Alzheimer's disease brains is not well studied. Scientists from the University of Kentucky and other institutions utilized a new technology to identify alterations in the glycan chains (https://www.creative-biolabs.com/glycoprotein/glycan-sequencing.htm) that attach to brain proteins in the bodies of deceased healthy people and patients with Alzheimer's disease.
Researchers have yet to discover a viable treatment for Alzheimer's disease, thus new approaches to preventing the disease progression are urgently needed. The researchers created a new imaging technology that identifies unique patterns of sugar molecule adsorbed to proteins inside tissues, according to the research. The researchers analyzed the N-glycosylation (https://www.creative-biolabs.com/glycoprotein/glycosylation-site-mapping...) pattern of sugar molecule adsorption, and they used this innovative technology to examine the "glycocode" in the brains of two mice with Alzheimer's disease and human subjects who died of dementia.
One model accumulated Aβ protein in their brains, while the other had accumulated Tau protein in their brains. Although they have different pathological mechanisms, all models show increased levels of N-glycosylation in the frontal cortex and hippocampus. In addition, the researchers analyzed three age-matched individuals and three patients with Aβ-type Alzheimer's disease, and as in the mouse brains, they had increased levels of glycosylation in their frontal cortex regions, however, in contrast to the results observed in the mouse organism, these patients had decreased levels of N-glycosylation in their hippocampal regions.
These findings reveal regional differences in the frontal cortex and hippocampus between human Alzheimer's disease patients and matched control individuals. Specifically, the researchers discovered increased levels of N-glycosylation in the frontal cortex and decreased levels of N-glycosylation in the hippocampal region of Alzheimer's disease patients' brains. In addition, this study highlights fundamental differences in N-chain protein glycosylation patterns in Alzheimer's disease patients' brains.
According to Tara Hawkinson, N-chain protein glycosylation is vital for both neurons and glial cells in the central nervous system, since it regulates numerous aspects of critical proteins involved in neuronal activity, whereas incorrect glycosylation causes improper neuronal function and death. As a result, altered protein glycosylation may cause a variety of neurological rolling caps, ranging from diseases characterized by neuronal loss, such as Alzheimer's disease and Parkinson's disease, to diseases characterized by neuronal connectivity defects, such as schizophrenia and developmental neurological disorders.
The novel approaches established by the researchers may be used to examine the spatial distribution of the glycocode of N-glycosylation patterns in the brain, allowing researchers to ask many critical questions, such as how these patterns are altered under pathological situations, as described in this work. "We can begin to answer questions about how brain cells coordinate glucose metabolism to balance the body's energy and glycosylation needs, and how changes in glycocode contribute to the development of neurological disorders, with these methodological advances, and researchers can begin to develop new methods to address these questions", according to researcher Gentry.
This study may point scientists in the direction of future research on therapeutic targets and biomarker assessments.
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