By Danielle Houghton
UF neuroscientist and associate professor, Jose Abisambra, Ph. D., makes considerable contributions to research exploring how chronic PERK (protein) induction promotes Alzheimer-like neuropathology in Down syndrome, leaving insights for therapeutic intervention.
Abisambra’s team identified the vast impact of a molecular pathway called ‘the unfolded protein response’ on Down syndrome (DS). “Our work highlights a unique protein called PERK, which is hyperactive in disease,” explains Abisambra. After the team inhibited PERK and modified disease outcomes, Abisambra and the team were most surprised to find that this mechanism is shared with Alzheimer’s disease (AD) and more than 20 other related disorders.
Identifying mechanisms in protein misfolding, which promotes cellular toxicity, is a major challenge in neurobiology. Many neurodegenerative disorders present the chronic activation of PERK, which leads to sustained reduction in protein synthesis and induction of cell death pathways. In investigating human DS frontal cortices, the team found this early and sustained PERK activation.
Abisambra, who focuses on pathogenic mechanisms of Alzheimer’s and related disorders, shares, “by their fourth decade of life, virtually all Down syndrome patients develop cognitive impairment and pathology that is similar to Alzheimer’s disease. There is no intervention that can stop the progression of dementia in these disorders. This study highlights a potential new therapeutic target that could overcome this tremendous challenge.”
The research findings reveals the importance in regulating the PERK pathway in DS in regard to cellular dysfunction, which actively contributes in the brain to the early development of AD.
Abisambra wants to tell people everywhere, “there is hope.” He explains that his teams and others are working in discovering new ways to intervene and improve the quality of life of millions people suffering from these types of dementia. “However, only scientific research can afford the ability to learn about ‘how’ diseases start and progress, and in doing so, identify ‘where’ we can intervene. This requires tremendous efforts to build technology, resources, time, and passionate individuals who love science and are motivated to make a difference,” says Abisambra.
His team is currently exploring ways to modify PERK as well as identifying new therapeutic interventions.