Nuclear factor‐kappa B (NF‐κB) in pathophysiology of Parkinson disease: Diverse patterns and mechanisms contributing to neurodegeneration

다국어 초록 (Multilingual Abstract)

Parkinson's disease (PD), the most common movement disorder, comprises several pathophysiologic mechanisms including misfolded alpha‐synuclein aggregation, inflammation, mitochondrial dysfunction, and synaptic loss. Nuclear Factor‐Kappa B (NF‐κB), as a key regulator of a myriad of cellular reactions, is shown to be involved in such mechanisms associated with PD, and the changes in NF‐κB expression is implicated in PD. Alpha‐synuclein accumulation, the characteristic feature of PD pathology, is known to trigger NF‐κB activation in neurons, thereby propagating apoptosis through several mechanisms. Furthermore, misfolded alpha‐synuclein released from degenerated neurons, activates several signaling pathways in glial cells which culminate in activation of NF‐κB and production of pro‐inflammatory cytokines, thereby aggravating neurodegenerative processes. On the other hand, NF‐κB activation, acting as a double‐edged sword, can be necessary for survival of neurons. For instance, NF‐κB activation is necessary for competent mitochondrial function and deficiency in c‐Rel, one of the NF‐κB proteins, is known to propagate DA neuron loss via several mechanisms. Despite the dual role of NF‐κB in PD, several agents by selectively modifying the mechanisms and pathways associated with NF‐κB, can be effective in attenuating DA neuron loss and PD, as reviewed in this paper.