Mounira Fayyad

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. It is caused by a progressive loss of dopaminergic neurons in the substantia nigra (SN) region of the brain. The most prominent symptoms of PD are resting tremors, rigidity, bradykinesia, and postural instability. A major pathological hallmark of the disease is the accumulation of Lewy Bodies (LBs) and Lewy Neurites (LNs), protein-rich inclusions that deposit in the neurons. These inclusions are mainly composed of alpha-synuclein (α-syn), a small protein with a propensity to aggregate. Evidence from genetic, biochemical and pathological studies suggest that the aggregation of α-syn plays a key role in the pathogenesis of PD and related disorders, such as dementia with Lewy Bodies (DLB) and multiple system atrophy (MSA), collectively termed synucleinopathies. Till date, the diagnosis of PD primarily depends on the clinical criteria, however, this approach has some limitations since the neurodegeneration starts several years before. This necessitates the development of reliable biomarkers that can allow early diagnosis of PD, preferably at the preclinical stage. Accumulative evidence suggests that majority of α-syn from LBs in the brains of PD patients is found to be phosphorylated at Serine 129, thus highlighting the importance of phosphorylated α-syn at S129 (pS129-α-syn) as a potential biomarker for PD. For this reason, we developed mouse monoclonal antibody (mAb) specific for pS129-α-syn and another mAb specific for non phosphorylated form of α-syn at S129 (nonpS129-α-syn). To our knowledge, this is the first study that reports the generation of an antibody specific for nonpS129-a-syn. In this study, we describe the production and thorough characterization of these two antibodies, highlighting that our antibodies represent useful tools for research, good candidates for biomarkers development, and even immunotherapy for PD and related disorders.

Date of Award	2017
Original language	American English
Awarding Institution	HBKU College of Health & Life Sciences