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Nuclear factor‐kappa B (NF‐κB) in pathophysiology of Parkinson disease: Diverse patterns and mechanisms contributing to neurodegeneration
Author(s) -
Dolatshahi Mahsa,
Ranjbar Hameghavandi Mohammad Hossein,
Sabahi Mohammadmahdi,
Rostamkhani Sabra
Publication year - 2021
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.15242
Subject(s) - neurodegeneration , nf κb , neuroscience , parkinson's disease , inflammation , alpha synuclein , microbiology and biotechnology , biology , nfkb1 , regulator , pathophysiology , signal transduction , disease , medicine , immunology , pathology , transcription factor , endocrinology , biochemistry , gene
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.