Title: MAO-B Elevation as an Early Parkinson’s Disease Biomarker and
Target for Prophylactic Treatment
Buck Institute Case No.: BI-377
Monoamine oxidase B (MAO-B) catalyzes the oxidative deamination of monoamines including
dopamine. MAO-B is mostly concentrated in the brain in astrocytes and astroglia. It has been postulated that age-related increases in MAO-B activity may contribute to cellular degeneration in the brain due to corresponding increases in the production of reactive oxygen species (ROS). Its expression levels are known to increase with age and in association with neurodegenerative disease in both humans and rodents. Although MAO-B is expressed primarily in astrocytes and not directly in dopaminergic cells, H2O2 has a high membrane permeability and therefore it can induce toxic effects not only within the cell of origin, but also in neighboring cells such as neurons which themselves have low endogenous antioxidant levels. MAO-B activity levels have been found to be doubled in the substantia nigra (SN), the area of the brain preferentially affected in Parkinson’s disease (PD). Due to the fact that MAO-B not only breaks down dopamine but also produces neurotoxic oxidative species, MAO-B inhibition is of significant interest as a therapeutic PD target.
There are numerous reports demonstrating the neuroprotective effects of MAO-B inhibition,
including target-specific therapeutics such as selegiline and rasagiline to treat PD. The suggestion has been made that these compounds may act as neuroprotectants via their actions as anti-oxidants rather than actual MAO-B inhibitors. Recent work by the Andersen Laboratory has demonstrated that astrocytic MAO-B elevation mimicking that occurring in aging and disease results in many pathological features of PD suggesting that MAO-B can directly contribute to these affects (Mallajoysyulla et al., 2008).
The Andersen Laboratory at the Buck Institute has contributed greatly to this area of PD research.
Through the use of novel biology, both in vitro
and in vivo
, the Andersen lab has identified two major findings related to this disease.
1. Novel Biomarkers – Parkinson’s patients are diagnosed when they become symptomatic. By
this time, 60-80% of nigrostriatal dopamine levels have been depleted. Since MAO-B expression levels have been found to inversely correlate with this loss, MAO-B may be a key biomarker in the neuropathological progression of the disease. The fact that MAO-B expression in various cells throughout the body appear to track with each other allows for
MAO-B expression in easily accessible blood platelets to be a strong candidate as a biomarker for not only the symptomatic but also the pre-symptomatic detection of PD.
2. Prophylactic Treatment – Given that PD may be detected pre-symptomatically via the
measurement of surrogate platelet MAO-B levels, the inhibition of MAO-B may slow or stabilize dopaminergic neuronal loss. Research has been done on halting this pre-symptomatic disease biology to address this phenomenon before it affects the patient (Siddiqui et al., 2010).
The Andersen Lab has published extensively on this subject. Re-prints can be made available upon request.
The Buck Institute is the only free-standing institute dedicated to aging and age-related research in the United States. We actively partner with industry to develop therapeutics, diagnostics or tools that make a difference. For more information on this or another technology or opportunity, please contact
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