Riederer P, et al. Exp Neurobiol. 2011 Mar;20(1):1-17. http://dx.doi.org/10.5607/en.2011.20.1.1

Monoamine oxidase inhibitors (MAO-I) have been useful in the treatment of both psychiatric and neurological disorders over centuries. Here we focus on the development of this drug treatment. Focus is given on the use of irreversible MAO-I's as well as on reversible ones. Benefit and side effects are reported for Parkinson's disease, Alzheimer's dementia, depression syndrome and panic disorders. The preclinical and clinical effects of selegiline with regard to neuroprotection are highlightened and the conclusion is drawn that there is good evidence for a clinical neuroprotective capacity based on the assumption that the 50 percent recovery of MAO-B is obtained already after a 10 days withdrawal of selegiline. There is also a focus on selegilines metabolism to amphetamine and metamphetamine. In order to avoid any such effects of metabolic compounds on the cardiovascular system Zydis Selegiline, a melt-tablet avoid of major metabolism to amphetamine and metamphetamine is described in detail. Developments in MAO-I research are discussed in detail as there are moclobemide, lacabemide, rasagiline. Interactions of MAO-I' with tricyclics and serotonin selective reuptake inhibitors (SSRI's) are described as there is mentioning of interactions of MAO-I's with other compounds in general. Tables and figures report on clinical studies and on pharmacological properties of MAO-I's.

The heterogeneity of Parkinson’s disease (PD), i.e. the various clinical phenotypes, pathological findings, genetic predispositions and probably also the various implicated pathophysiological pathways pose a major challenge for future research projects and therapeutic trail design. We outline several pathophysiological concepts, pathways and mechanisms, including the presumed roles of α-synuclein misfolding and aggregation, Lewy bodies, oxidative stress, iron and melanin, deficient autophagy processes, insulin and incretin signaling, T-cell autoimmunity, the gut–brain axis and the evidence that microbial (viral) agents may induce molecular hallmarks of neurodegeneration. The hypothesis is discussed, whether PD might indeed be triggered by exogenous (infectious) agents in susceptible individuals upon entry via the olfactory bulb (brain first) or the gut (body-first), which would support the idea that disease mechanisms may change over time. The unresolved heterogeneity of PD may have contributed to the failure of past clinical trials, which attempted to slow the course of PD. We thus conclude that PD patients need personalized therapeutic approaches tailored to specific phenomenological and etiologic subtypes of disease.

Background: The search for biomarkers in Parkinson’s disease (PD) is crucial to identify the disease early and monitor the effectiveness of neuroprotective therapies. We aim to assess whether a gene signature could be detected in blood from early/mild PD patients that could support the diagnosis of early PD, focusing on genes found particularly altered in the substantia nigra of sporadic PD. Results: The transcriptional expression of seven selected genes was examined in blood samples from 62 early stage PD patients and 64 healthy age-matched controls. Stepwise multivariate logistic regression analysis identified five genes as optimal predictors of PD: p19 S-phase kinase-associated protein 1A (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.60–0.90), huntingtin interacting protein-2 (OR 1.32; CI 1.08–1.61), aldehyde dehydrogenase family 1 subfamily A1 (OR 0.86; 95% CI 0.75–0.99), 19 S proteasomal protein PSMC4 (OR 0.73; 95% CI 0.60–0.89) and heat shock 70-kDa protein 8 (OR 1.39; 95% CI 1.14–1.70). At a 0.5 cut-off the gene panel yielded a sensitivity and specificity in detecting PD of 90.3 and 89.1 respectively and the area under the receiving operating curve (ROC AUC) was 0.96. The performance of the five-gene classifier on the de novo PD individuals alone composing the early PD cohort (n = 38), resulted in a similar ROC with an AUC of 0.95, indicating the stability of the model and also, that patient medication had no significant effect on the predictive probability (PP) of the classifier for PD risk. The predictive ability of the model was validated in an independent cohort of 30 patients at advanced stage of PD, classifying correctly all cases as PD (100% sensitivity). Notably, the nominal average value of the PP for PD (0.95 (SD = 0.09)) in this cohort was higher than that of the early PD group (0.83 (SD = 0.22)), suggesting a potential for the model to assess disease severity. Lastly, the gene panel fully discriminated between PD and Alzheimer’s disease (n = 29). Conclusions: The findings provide evidence on the ability of a five-gene panel to diagnose early/mild PD, with a possible diagnostic value for detection of asymptomatic PD before overt expression of the disorder.