There was also a panel discussion centered on the role of the gut microbiome in brain function and neuroinflammation, and a heartbreaking talk about a rare disease, called Multiple System Atrophy (MSA), that appears to be linked to neuroinflammation.
(Proceeds from Charles River symposium were donated to the Multiple System Atrophy Coalition, which assists researchers in finding a cure and provides support to patients and caregivers.) If there was a common thread among all of these talks it was that better drugs are needed for diseases of the central nervous system, and that inflammatory processes in the brain and spinal cord, prominent in many of CNS conditions, are a good place to look.
“Maybe different strains, different conformations of alpha synuclein will lead to different diseases,” he said.
Khurana also noted that lysates from the brains of MSA patients look strikingly different from the lysed cells of people with PD or Lewy body dementia.
The kinase LRRK2, which has been genetically linked to development of PD and is now a hot therapeutic target by a number of labs, had much earlier been associated with Crohn’s disease and inflammatory bowel disease.
According to Tansy, it could be that infection or some other assault in the gut might trigger inflammatory responses that then upregulate levels of alpha-synuclein in surrounding nerve cells that are part of the enteric system.
But this rare disease—only about 1,900 cases are diagnosed yearly in the US—is quite distinct from PD, noted Vikram Khurana, MD, Ph D, Chief of the Division of Movement Disorders at Brigham & Women’s Hospital, which is developing treatments for both MSA and PD.
One of the biological differences, says Khurana, is where alpha-synuclein accumulates. In MSA, it is primarily in oligodendrocytes, which produce the myelin sheath that electrically insulates axons.
Tansey said the study, led by Emory graduate student Madelyn Houser, found elevated levels of three inflammatory molecules—vascular endothelial growth factor receptor 1, interleukin-1α, and CXCL8—in the stool samples of PD patients compared to matched controls.Oligodendrocytes are also glia cells, which perform a role similar to that of the peripheral immune system, and can also contribute to exaggerated pain responses.Khurana said there is now growing interest in how distinct proteins cause different conformations (variants) within different cells types and cause different diseases.the genetic regulation of neural mechanisms, and their modulation by environmental circumstances, that impact upon cognitive function, cognitive reserve and flexibility, learning, and memory; 8) Studies to investigate gene by environmental covariation.pathways by which the built environment exerts influence on persons with functional disabilities and on diverse health outcomes such as infant morbidity and mortality, asthma, perturbations of the immune system, degenerative or developmental neurologic disorders, cognitive disorders, behavioral disorders, sensory impairment, and cardiovascular disease; Ficino's commentaries for the past twenty years, assures their scholarly weight and reliability, while making the volume itself, faultlessly executed and most reasonably priced by California, one of the last great bargains of the waning twentieth century.