PMID- 37210624
OWN - NLM
STAT- MEDLINE
DCOM- 20230704
LR  - 20230705
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 27
IP  - 13
DP  - 2023 Jul
TI  - NF-kappaB/NLRP3 inflammasome axis and risk of Parkinson's disease in Type 2 diabetes 
      mellitus: A narrative review and new perspective.
PG  - 1775-1789
LID - 10.1111/jcmm.17784 [doi]
AB  - 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-kappaB) and the nod-like receptor pyrin 3 (NLRP3) inflammasome. NF-kappaB is 
      implicated in the pathogenesis of T2DM, and activation of NF-kappaB with induction of 
      neuronal apoptosis was also confirmed in PD patients. Systemic activation of 
      NLRP3 inflammasome promotes the accumulation of alpha-synuclein and degeneration of 
      dopaminergic neurons in the SN. Increasing alpha-synuclein in PD patients enhances 
      NLRP3 inflammasome activation and the release of interleukin (IL)-1beta followed by 
      the development of systemic inflammation and neuroinflammation. In conclusion, 
      activation of the NF-kappaB/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 beta-cell dysfunction and the 
      development of T2DM. Therefore, attenuation of inflammatory changes by inhibiting 
      the NF-kappaB/NLRP3 inflammasome axis in the early T2DM may reduce future PD risk.
CI  - (c) 2023 The Authors. Journal of Cellular and Molecular Medicine published by 
      Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
FAU - Alrouji, Mohammed
AU  - Alrouji M
AD  - Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, 
      Shaqra University, Shaqra, Saudi Arabia.
FAU - Al-Kuraishy, Hayder M
AU  - Al-Kuraishy HM
AD  - Department of Clinical Pharmacology and Medicine, College of Medicine, 
      ALmustansiriyia University, Baghdad, Iraq.
FAU - Al-Gareeb, Ali I
AU  - Al-Gareeb AI
AD  - Department of Clinical Pharmacology and Medicine, College of Medicine, 
      ALmustansiriyia University, Baghdad, Iraq.
FAU - Alexiou, Athanasios
AU  - Alexiou A
AUID- ORCID: 0000-0002-2206-7236
AD  - Department of Science and Engineering, Novel Global Community Educational 
      Foundation, Hebersham, New South Wales, Australia.
AD  - AFNP Med, Wien, Austria.
FAU - Papadakis, Marios
AU  - Papadakis M
AD  - Department of Surgery II, University Hospital Witten-Herdecke, University of 
      Witten-Herdecke, Wuppertal, Germany.
FAU - Jabir, Majid S
AU  - Jabir MS
AD  - Applied Science Department, University of Technology, Baghdad, Iraq.
FAU - Saad, Hebatallah M
AU  - Saad HM
AUID- ORCID: 0000-0001-9555-7300
AD  - Department of Pathology, Faculty of Veterinary Medicine, Matrouh University, 
      Matrouh, Egypt.
FAU - Batiha, Gaber El-Saber
AU  - Batiha GE
AD  - Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, 
      Damanhour University, Damanhour, Egypt.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20230521
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Inflammasomes)
RN  - 0 (NF-kappa B)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (alpha-Synuclein)
RN  - 0 (Pyrin)
RN  - 0 (NLR Proteins)
SB  - IM
MH  - Humans
MH  - Inflammasomes/metabolism
MH  - NF-kappa B/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - alpha-Synuclein
MH  - *Parkinson Disease/metabolism
MH  - Pyrin
MH  - NLR Proteins
MH  - *Neurodegenerative Diseases
MH  - Neuroinflammatory Diseases
MH  - *Diabetes Mellitus, Type 2/complications
PMC - PMC10315781
OTO - NOTNLM
OT  - NF-kappaB
OT  - NLRP3 inflammasome
OT  - Parkinson disease
OT  - T2DM
COIS- The authors declare no conflict of interest.
EDAT- 2023/05/21 06:42
MHDA- 2023/07/04 06:42
PMCR- 2023/05/21
CRDT- 2023/05/21 03:43
PHST- 2023/04/27 00:00 [revised]
PHST- 2022/12/07 00:00 [received]
PHST- 2023/05/10 00:00 [accepted]
PHST- 2023/07/04 06:42 [medline]
PHST- 2023/05/21 06:42 [pubmed]
PHST- 2023/05/21 03:43 [entrez]
PHST- 2023/05/21 00:00 [pmc-release]
AID - JCMM17784 [pii]
AID - 10.1111/jcmm.17784 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2023 Jul;27(13):1775-1789. doi: 10.1111/jcmm.17784. Epub 2023 May 
      21.