Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Jul;27(13):1775-1789.
doi: 10.1111/jcmm.17784. Epub 2023 May 21.

NF-κB/NLRP3 inflammasome axis and risk of Parkinson's disease in Type 2 diabetes mellitus: A narrative review and new perspective

Mohammed Alrouji  1 , Hayder M Al-Kuraishy  2 , Ali I Al-Gareeb  2 , Athanasios Alexiou  3   4 , Marios Papadakis  5 , Majid S Jabir  6 , Hebatallah M Saad  7 , Gaber El-Saber Batiha  8
Affiliations
Review

NF-κB/NLRP3 inflammasome axis and risk of Parkinson's disease in Type 2 diabetes mellitus: A narrative review and new perspective

Mohammed Alrouji et al. J Cell Mol Med. 2023 Jul.

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD). Genetic predisposition and immune dysfunction are involved in the pathogenesis of PD. Notably, peripheral inflammatory disorders and neuroinflammation are associated with PD neuropathology. Type 2 diabetes mellitus (T2DM) is associated with inflammatory disorders due to hyperglycaemia-induced oxidative stress and the release of pro-inflammatory cytokines. Particularly, insulin resistance (IR) in T2DM promotes the degeneration of dopaminergic neurons in the substantia nigra (SN). Thus, T2DM-induced inflammatory disorders predispose to the development and progression of PD, and their targeting may reduce PD risk in T2DM. Therefore, this narrative review aims to find the potential link between T2DM and PD by investigating the role of inflammatory signalling pathways, mainly the nuclear factor kappa B (NF-κB) and the nod-like receptor pyrin 3 (NLRP3) inflammasome. NF-κB is implicated in the pathogenesis of T2DM, and activation of NF-κB with induction of neuronal apoptosis was also confirmed in PD patients. Systemic activation of NLRP3 inflammasome promotes the accumulation of α-synuclein and degeneration of dopaminergic neurons in the SN. Increasing α-synuclein in PD patients enhances NLRP3 inflammasome activation and the release of interleukin (IL)-1β followed by the development of systemic inflammation and neuroinflammation. In conclusion, activation of the NF-κB/NLRP3 inflammasome axis in T2DM patients could be the causal pathway in the development of PD. The inflammatory mechanisms triggered by activated NLRP3 inflammasome lead to pancreatic β-cell dysfunction and the development of T2DM. Therefore, attenuation of inflammatory changes by inhibiting the NF-κB/NLRP3 inflammasome axis in the early T2DM may reduce future PD risk.

Keywords: NF-κB; NLRP3 inflammasome; Parkinson disease; T2DM.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Pathophysiology of PD.
FIGURE 2
FIGURE 2
T2DM and associated inflammatory disorders.
FIGURE 3
FIGURE 3
PD and inflammatory disorders.
FIGURE 4
FIGURE 4
The mutual relationship between T2DM and PD.
FIGURE 5
FIGURE 5
NF‐κB signalling pathway is activated in both T2DM and PD.
FIGURE 6
FIGURE 6
NLRP3 inflammasome is involved in the pathogenesis and complications of T2DM.
FIGURE 7
FIGURE 7
α‐synuclein triggers the activation of the NLRP3 inflammasome with subsequent release of IL‐1β and the development of systemic inflammation and neuroinflammation.
FIGURE 8
FIGURE 8
T2DM‐induced hyperglycaemia promotes the activation of the NLRP3 inflammasome and neuroinflammation leading to the development of PD.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Poewe W, Seppi K, Tanner CM, et al. Parkinson disease. Nat Rev Dis Primers. 2017;3(1):1‐21. - PubMed
    1. Xiao‐dan W, Yong J. A 200‐year history of Parkinson's disease. Chin J Contemp Neurol Neurosurg. 2017;17(1):5.
    1. Varalta V, Picelli A, Fonte C, et al. Relationship between cognitive performance and motor dysfunction in patients with Parkinson's disease: a pilot cross‐sectional study. Biomed Res Int. 2015;2015:1‐6. - PMC - PubMed
    1. Poewe W. Non‐motor symptoms in Parkinson's disease. Eur J Neurol. 2008;15:14‐20. - PubMed
    1. Park J‐H, Kim D‐H, Kwon D‐Y, et al. Trends in the incidence and prevalence of Parkinson's disease in Korea: a nationwide, population‐based study. BMC Geriatr. 2019;19(1):1‐10. - PMC - PubMed

Publication types

-