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

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease and the most common movement disorder, which causes morbidity and mortality and imposes a large burden (Kowal et al., 2013). Sporadic form of PD occurs more abundantly in aging population and causes symptoms like rigidity, bradykinesia, akinesia, resting tremor, motor imbalance, etc (Davie, 2008). It is characterized by selective degeneration and progressive loss of dopaminergic (DA) neurons in substantia nigra pars compacta (SNpc) which give rise to axonal processes innervating striatum (Surmeier, 2018). A myriad of etiologies contribute to DA neuron loss including inflammation, oxidative stress, autophagy, neurotransmission alterations, metabolic changes, etc. However, the

Identification of structural features of selected flavonoids responsible for neuroprotection using a Drosophila model of Parkinson’s disease

“…In addition, relish knockdown leads to improved survival, climbing ability and rescue of dopaminergic neurons against PQ-mediated toxicity in Drosophila (39). Consistent with these findings, increased NFB activation has been linked to PD pathogenesis in diverse mammalian models (52)(53)(54)(55). Therefore, we next determined the effect of flavones on the transcript levels of relish.…”

Human neural stem cell-derived extracellular vesicles protect against Parkinson’s disease pathologies

“…S4) were inferred as a result of decreased microglial activity. Also, the inflammatory cytokines (TNF-a, IL-1b, IL-6, IL-12, IL-1) and chemokine (CCL2, CXCL10), which are known as downstream factors of nuclear factor-kappa B (NF-κB), were attenuated after the administration of F3-derived EVs compared to LPS group [ 33 ]. Through these results, it can be considered that the NF-κB pathway effectively reduced through F3-derived EVs as a mechanism of astrocyte reactivity induced by 6-OHDA.…”

Nutraceuticals as Modulators of Autophagy: Relevance in Parkinson’s Disease

“…NF-κB (nuclear factor kappa B) is, in addition to TFEB and Nrf2, yet another transcription factor that has been proposed as a potential therapeutic target of PD. It is a ubiquitously expressed transcription factor that is responsible for maintaining cell survival, proliferation, activation of some of the anti-apoptotic pathways, and cellular response to inflammation [ 41 ]. Due to its multifunctionality, the involvement of NF-κB in pathways that relate to NDs is somewhat impressive: it has been reported to interact via TLRs (toll-like receptors), GSK-3β (glycogen synthase kinase 3β) and PI3K/Akt pathway, p38-MAPK pathway, and many more [ 41 ].…”

“…It is a ubiquitously expressed transcription factor that is responsible for maintaining cell survival, proliferation, activation of some of the anti-apoptotic pathways, and cellular response to inflammation [ 41 ]. Due to its multifunctionality, the involvement of NF-κB in pathways that relate to NDs is somewhat impressive: it has been reported to interact via TLRs (toll-like receptors), GSK-3β (glycogen synthase kinase 3β) and PI3K/Akt pathway, p38-MAPK pathway, and many more [ 41 ]. Furthermore, the absence of Nrf2 leads to the induction of NF-κB-dependent processes that promote neurodegeneration [ 42 ], albeit the presence of Nrf2 protects against MPTP-induced neurodegeneration via suppression of the NF-κB and p38/MAPK signaling pathways [ 43 , 44 ].…”