Pharmacological therapy in Parkinson's disease: focus on neuroprotection

Abstract

Although the number of available therapeutic approaches in Parkinson's disease (PD) is steadily increasing the search for effective neuroprotective agent is continuing. Such research is directed at influencing the key steps in the pathomechanism: the mitochondrial dysfunction, the oxidative stress, the neuroinflammatory processes and the final common apoptotic pathway. Earlier-developed symptomatic therapies were implicated to be neuroprotective, and promising novel disease modifying approaches were brought into the focus of interest. The current review presents a survey of our current knowledge relating to the pathomechanism of PD and discusses the putative neuroprotective therapy.

Figure 1

Interaction of pathomechanical pathways in PD.

Figure 2

Apoptotic processes in PD. Extrinsic pathway initiated from the cell surface receptors (e.g., Fas) and proceeding through a cascade of events, in which caspases are involved. The activation of the intrinsic pathway begins with the permeabilization of the mitochondrial outer membrane, which leads to the release of key mitochondrial proteins (such as cytochrome c, Smacs, AIF, etc.). Members of the Bcl2 family of proteins are important modulators of pro‐ and antiapoptotic mechanisms. The inset shows the structure of the mitochondrion and the respiratory chain (JNK, c‐Jun N‐terminal kinase; Smacs, secondary mitochondria‐derived activator caspases; AIF, apoptosis inducing factor; Apaf‐1, apoptotic peptidase activating factor 1).

Figure 3

The kynurenine pathway of the tryptophan metabolism.