Title:Nuclear Factor Kappa B: A Nobel Therapeutic Target of Flavonoids
Against Parkinson's Disease
Volume: 27
Issue: 14
Author(s): Niraj Kumar Singh*, Ashini Singh and Mayank
Affiliation:
- Division of Pharmacology, Institute of Pharmaceutical Research, GLA University, Mathura-281406, UP, India
Keywords:
Parkinson’s disease, NF-κB, neuroinflammation, flavonoid, neuroprotection, SNpc.
Abstract: Parkinson's disease (PD), the most common brain-related neurodegenerative disorder,
is comprised of several pathophysiological mechanisms, such as mitochondrial dysfunction, neuroinflammation,
aggregation of misfolded alpha-synuclein, and synaptic loss in the substantia
nigra pars compacta region of the midbrain. Misfolded alpha-synuclein, originating from damaged
neurons, triggers a series of signaling pathways in both glial and neuronal cells. Activation
of such events results in the production and expression of several proinflammatory cytokines via
the activation of the nuclear factor κB (NF-κB) signaling pathway. Consequently, this cascade of
events worsens the neurodegenerative processes, particularly in conditions, such as PD and
synucleinopathies. Microglia, astrocytes, and neurons are just a few of the many cells and tissues
that express the NF-κB family of inducible types of transcription factors. The dual role of NF-κB
activation can be crucial for neuronal survival, although the classical NF-κB pathway is important
for controlling the generation of inflammatory mediators during neuroinflammation.
Modulating NF-κB-associated pathways through the selective action of several agents holds
promise for mitigating dopaminergic neuronal degeneration and PD. Several naturally occurring
compounds in medicinal plants can be an effective treatment option in attenuating PD-associated
dopaminergic neuronal loss via selectively modifying the NF-κB-mediated signaling pathways.
Recently, flavonoids have gained notable attention from researchers because of their remarkable
anti-neuroinflammatory activity and significant antioxidant properties in numerous neurodegenerative
disorders, including PD. Several subclasses of flavonoids, including flavones, flavonols,
isoflavones, and anthocyanins, have been evaluated for neuroprotective effects against in
vitro and in vivo models of PD. In this aspect, the present review highlights the pathological role
of NF-κB in the progression of PD and investigates the therapeutic potential of natural flavonoids
targeting the NF-κB signaling pathway for the prevention and management of PD-like
manifestations with a comprehensive list for further reference. Available facts strongly support
that bioactive flavonoids could be considered in food and/or as lead pharmacophores for the
treatment of neuroinflammation-mediated PD. Furthermore, natural flavonoids having potent
pharmacological properties could be helpful in enhancing the economy of countries that cultivate
medicinal plants yielding bioactive flavonoids on a large scale.
