CATECHOLAMINE REGULATED PROTEIN 40 (CRP40): CLINICAL IMPLICATIONS IN PARKINSON’S DISEASE

Abstract

<p>Parkinson’s disease (PD) is characterized by progressive cell death of the dopaminergic neurons of nigrostriatal pathway. Several causes have been implicated for PD via neurochemical research including mitochondrial dysfunction, oxidative stress, and protein misfolding, to list a few. The novel Catecholamine Regulated Protein 40 (CRP40) has certain dopaminergic and neuroprotective features that implicate its importance for PD research. Recent studies using post-mortem brain tissue of patients with PD found MOT-2/CRP40 depletion in the frontal cortex and substantia nigra. MOT-2/CRP40 reduction is also observed in striatal brain tissue samples from a hemi-lesioned preclinical animal model of PD. Most recently, work done at the University of Laval in collaboration McMaster University suggests that levels of CRP40 mRNA are in deficit in blood platelet samples from a primate model of PD.</p> <p>The studies presented in this thesis suggest that the CRP40 protein has a dual function with regards to PD. The full-length CRP40 binds dopamine and, upon injection at the striatum of 6-hydroxydopamine hemi-lesioned rats, alleviates behavioural symptoms for up to 7 days. On the other hand, a 7kDA fragment of CRP40 does not bind dopamine, but does confer the same alleviatory effect upon intra-striatal injection in 6-hydroxydopamine hemi-lesioned rats. Not only has a protein now been identified with novel potential as a therapeutic agent for PD, but also the approximate region of the CRP40 protein responsible for behavioural effects.</p> <p>The later studies of this thesis show that CRP40 is found dysregulated in platelets of PD patients and lymphocytes of SCZ patients. This evidence has revealed CRP40 as a novel PD biomarker, for which on going studies are now in place to explore the potential of CRP40 as a diagnostic for PD.</p>