Therapeutic Approaches for PD

Like AD, neurochemical changes in PD appear many years before the appearance of the first cognitive alterations in PD patients and PD is diagnosed late life only after substantial neurodegeneration in substantia nigra pars compacta has occurred. Although the molecular mechanisms associated with the pathogenesis of PD are 

Choice of pharmacotherapy includes consideration of short-term benefits as well as long-term consequences. Patients with mild PD often function adequately without symptomatic treatment. However, therapeutic approaches that are commonly used at the present time include dopaminergic strategies, antioxidant and anti-inflammatory strategies, stabilization of mitochondrial dynamics, use of statins, memantine, co-3 fatty acids, and gene therapy (Farooqui, 2009a). 

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In this chapter a number of approaches will be discussed that have been developed to address the challenges in macromolecule drag assays that impact upon selectivity, accuracy, and precision. The most commonly used methods for pro-tein/peptide drags - IA and LC-MS/MS - are discussed in detail, with case studies to illustrate the process, issues, assay approaches, and method limitations. Other less common methods and emerging technologies will be briefly mentioned. Biologic therapeutics that are not pure and/or not well characterized pose extra challenges which are beyond the scope of this chapter. Neither will biomarker assays used to support pharmacodynamic (PD) studies be covered in this chapter. 

Physiologically based phannacokinetic/pharmacodynamic (PBPK/PD) modeling has proven useful in many areas of toxicology and therapeutics. This quantitative, mechanism-based approach has allowed limited experimental in vivo and in vitro data to be quantitatively integrated with physiological data so as to facilitate predictions of the behavior of organisms under different exposure conditions. Specifically, it has been used for ... 

New modalities in genomics, proteomics, and imaging have allowed monitoring of these effects and provide new directives for the future. All together, we provide a balanced review for the role of immunity in the pathogenesis of PD and ALS and the means to modulate it for therapeutic benefit. The strengths and concerns for each of these approaches are discussed. 

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