2022 Alzheimer's Association Clinician Scientist Fellowship (AACSF)

CGRP Pathways in Clinicopathogically -established Parkinson Disease

Can a certain protein fragment help prevent the brain inflammation and protein build-up linked to Parkinson’s disease?

Athanasia Alexoudi, Ph.D.
Neurological Institute of Athens
Athens, Greece

Background

Parkinson’s disease, the second most common cause of dementia behind Alzheimer’s, is characterized by specific brain changes, including the accumulation of alpha-synuclein protein. Alpha-synuclein is thought to help maintain proper nerve cell communication in the brain. In Parkinson’s, however, this protein becomes modified (or “misfolded”) and contributes to protein clumps called Lewy bodies.
 
According to recent studies, alpha-synuclein clumping may be related to brain inflammation caused by special protein clumps called inflammasomes. Studies have also found that a protein fragment called Calcitonin Gene-Related Peptide (CGRP) can activate molecular mechanisms (or “pathways”) that prevent inflammation. Taken together, these findings suggest CGRP may help prevent the alpha-synuclein build-up that leads to Parkinson’s by reducing inflammasome activity.

Research Plan

Dr. Athanasia Alexoudi and colleagues will recruit 40 individuals , 20 with clinically-diagnosed Parkinson’s disease and 20 without Parkinson’s. They will conduct extensive medical analyses of the participants, including assessments over time of memory, brain structure, motor skills and psychiatric symptoms. They will also measure blood and skin levels of CGRP and various inflammatory (inflammation-related) proteins, both before and after sleep. Such measurements will indicate how levels of these proteins change over time in the brain. The researchers will then identify how CGRP changes impact inflammatory protein levels in individuals with and without Parkinson’s. They will also examine how changes in CGRP levels during sleep may be linked to disease-related changes in motor skills, memory and other functions. Lastly, the investigators will use computer science techniques to test whether various Parkinson’s medications impact CGRP function and reduce brain inflammation in their participants.

Impact

Results from this study could shed new light on how inflammation promotes the development of Parkinson’s disease. They could also point to novel ways of repurposing currently-approved Parkinson’s disease medications to target CGRP and better treat the disorder.