Luis De La Rosa

Luis De La Rosa

Immune system and α-synuclein pathology in Parkinson's Disease

Authors

Luis De La Rosa, Elsa Gonzalez De la cruz, Paramita Chakrabarty

Mentor

Assistant Professor, Paramita Chakrabarty

College

College of Medicine

Abstract

<p>α-Synuclein​ is a presynaptic neuronal protein bound to membranes with an a-helical secondary structure. It is a major component of Lewy bodies and Lewy neurites​ which are Intracellular aggregates of α-Syn that represent a hallmark of synucleinopathies within Parkinson’s disease(PD). ​PD is a disorder that is identified by both motor features such as tremors, bradykinesia, and rigidity, and other non-motor features. PD is currently the world’s second most common age-associated neurodegenerative disorder, second only to Alzheimer’s disease. Research on PD has determined several Hallmark characteristics of the disease such as the loss of dopaminergic neurons in the substantia nigra (SN), intraneuronal aggregation of α- synuclein (αSyn), neuroinflammation, and gliosis. It is currently believed that the pathological aggravation of α-synuclein protein may be one of the processes responsible for the Neurodegeneration seen in PD. This study is aimed to determine the relationship between α-synuclein and neuroinflammation as we look into the role that immune cells play in PD. By using a transgenic mouse model that expresses a mutant α-synuclein protein, known as Line M83 mice, we were then able to create two new models of mice. The first which is deficient in the Rag1 allele has no B cells or T-cells. And the second is deficient in the MhcII allele which induces a faulty immune function due to the lack of T cells. Both of these were then injected with α-synuclein aggregates. By looking at the time it took for the mice to reach hind limb paralysis and by collecting brain and spinal cord tissues from these mice, we were able to analyze the effects of synuclein protein and the changes in immune cells on the brain. We were able to determine that the mice deficient in the rag1 allele showed no differences and were similar to the normal line of M83 mice. The mice model lacking the MhcII allele showed a shorter time to hind leg paralysis than the normal M83 mice. This data suggests that removing B & T cells does not affect how α-synuclein protein gets misfolded and causes diseases. it also shows us that microglia, which is a key immune cell inside the central nervous system, is an important factor in the maintenance of a healthy immune system. </p>

Poster

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