Abstract:

The role and involvement of Nogo-A in Parkinson’s disease (PD) is just beginning to evolve. Even though none of the Nogo-A signaling genes has been associated with PD, the results from animal studies showing that DAergic neurons co-expressing Nogo-A survive better in the later course of PD as well as more pronounced DAergic cell death in PD Nogo-A knock-out animals hint strongly to a neuroprotective role of Nogo-A in DAergic neurons. Moreover, Nogo-A knock-out mice have a better motor coordination as well as an enhanced locomotor reaction to systemic amphetamine injections compared to wild type mice. The function of Nogo-A in DAergic neurons, however, needs to be further elucidates especially with focus on its signaling. After all, other studies showed that LINGO-1 is increased in animal models of PD and hampered the survival of DAergic neurons. Moreover, antagonization of NgR1 or LINGO-1 led to significant increase in survival of DAgeric neurons, showing that the NgR1 complex has a negative regulatory role on the survival of DAergic neurons. Considering these findings, the potential neuroprotective role of Nogo-A in PD is probably not due to the Nogo-66 domain that signals through the NgR1 complex. Yet, if and how Nogo-A protects DAergic neurons from toxic insults and if there are other myelin associated proteins that act through the NgR1complex as negative regulator of DAergic neuron survival needs to be further investigated.