Development of efficacious treatments for Parkinson's disease (PD) demands an improved understanding of mechanisms underlying neurodegeneration. Two cellular death pathways postulated to play key roles in PD are autophagy and apoptosis. Molecular overlap between these pathways was investigated through identifying studies that used therapeutic compounds to alter expression of specific molecular components of the pathways. Bcl-2 was identified as an important protein with the ability to suppress autophagy and apoptosis through inhibiting Beclin-1 and Bax, respectively. Involvement of c-Jun N-terminal kinases (JNK) and p38, was evident in the activation of apoptosis through increasing the Bax/Bcl-2 ratio. JNK-mediated phosphorylation also suppresses the inhibiting functions of Bcl-2, indicating an ability to induce not only apoptosis but also autophagy. Additionally, a p38-mediated increase in heme oxygenase-1 expression inhibits apoptosis. Moreover, besides inhibiting mammalian target of rapamycin, Akt is associated with decreased Bax expression, thereby acting as both an autophagy inducer and apoptosis inhibitor. Ultimately, manipulation of molecular components involved in autophagy and apoptosis regulation could be targeted as possible therapies for PD.
Keywords: Apoptosis; Autophagy; Bcl-2; Parkinson's disease; Therapy.
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