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Category: neuroscience – Page 228

CHIP and aging: a key regulator of proteostasis and cellular senescence

Degradation of proteostasis, mitochondrial function, and cellular stress resistance results in a build-up of damaged proteins, oxidative insult, and chronic inflammation, characteristic of aging. CHIP is essential for maintaining protein quality control and cellular homeostasis by having dual E3 ubiquitin ligase and co-chaperone activities. CHIP facilitates proteostasis by maintaining proteostasis in misfolded, aggregated proteins by promoting their degradation. Mitochondrial dysfunction, oxidative imbalance, and cellular senescence are caused by its age-associated decline and contribute to neurodegenerative, cardiovascular, and oncogenic disease pathogenesis. Examples of recent pharmacological and gene-based strategies to correct CHIP and restore stress resilience have been made.

Protein aggregation is linked to altered RNA processing

Neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease, are devastating and incurable diseases. Although many neurodegenerative diseases are characterized by abnormal protein aggregation in the brain, a limited understanding of whether and how aggregated proteins cause brain cell dysfunction and death represents a major barrier to developing effective treatments.

Inspired by similar approaches in cardiovascular disease and cancer, the researchers focused on rare genetic forms of neurodegeneration as a powerful way to uncover fundamental mechanisms tying protein aggregation to brain disease. Thier work unexpectedly linked protein aggregation in genetic forms of neurodegeneration to disrupted processing of transfer RNAs (tRNAs), revealing an important mechanism that might be therapeutically targeted in these disorders.

The authors were interested in genetic forms of neurodegeneration caused by GGC trinucleotide repeat expansions (DNA sequence mutations caused by copying this 3-letter sequence too many times in a row). These mutations produce aggregation-prone proteins with long stretches of a single repeated amino acid (glycine).

Psychologists introduce third path to ‘good life’—one full of curiosity and challenge

New research suggests that psychological richness—a life of perspective-changing experiences—may matter just as much as happiness or meaning.

For centuries, scholars and scientists have defined the “good life” in one of two ways: a life that is rooted in , characterized by , or one that is centered on meaning, guided by purpose and personal fulfillment. But what if there is another, equally valuable path—one that prioritizes challenge, change and curiosity?

This , which may result in a more psychologically rich life for some, is being explored in a new study published in Trends in Cognitive Sciences, led by University of Florida psychologist Erin Westgate, Ph.D., in collaboration with Shigehiro Oishi, Ph.D., of the University of Chicago. According to their research, some people prioritize variety, novelty, and intellectually stimulating experiences, even when those experiences are difficult, unpleasant, or lack clear meaning.

A common food additive solves a sticky neuroscience problem

An interdisciplinary team working on balls of human neurons called organoids wanted to scale up their efforts and take on important new questions. The solution was all around them.

For close to a decade now, the Stanford Brain Organogenesis Program has spearheaded a revolutionary approach to studying the brain: Rather than probe intact brain tissues in humans and other animals, they grow three-dimensional brain-like tissues in the lab from , creating models called human neural organoids and assembloids.

Beginning in 2018 as a Big Ideas in Neuroscience project of Stanford’s Wu Tsai Neurosciences Institute, the program has brought together neuroscientists, chemists, engineers, and others to tackle the neural circuits involved in pain, genes that drive neurodevelopmental disorders, new ways to study brain circuits, and more.

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