Can NLRP3 (Nucleotide-binding domain, Leucine-rich Repeat-containing family, Pyrin domain-containing 3) activation lead to peripheral neuropathy?

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From the Research

NLRP3 Activation and Peripheral Neuropathy

• NLRP3 activation has been linked to various neurological disorders, including peripheral neuropathy 1, 2, 3.
• The activation of NLRP3 inflammasome contributes to neuroinflammation, which is a key pathogenic factor of secondary nerve injury in diabetes 1.
• NLRP3 inflammasome is an inducer of innate immune responses, and its activation stimulates the inflammatory cascade reaction, promotes the release of inflammatory mediators, and triggers cell death and uncontrolled autophagy 1, 2.
• The involvement of NLRP3 inflammasome in peripheral neuropathic pain has been explored, and it is suggested that NLRP3 inflammasome may represent a novel target for pain therapeutic development 3.

Mechanisms of NLRP3 Activation

• NLRP3 inflammasome can sense and be activated by a wide range of exogenous and endogenous stimuli, such as microbes, aggregated and misfolded proteins, and adenosine triphosphate 2, 4.
• The activation of NLRP3 inflammasome leads to the processing of pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and interleukin-18 (IL-18), which drive inflammatory responses and lead to neuronal damage 2, 4.
• MicroRNAs (miRNAs) have been identified as important regulators of NLRP3 inflammasome, and they may play a role in modulating neuropathic pain development and maintenance 3.

Association with Peripheral Neuropathy

• NLRP3 inflammasome activation has been linked to peripheral arterial disease (PAD), which is characterized by vascular inflammation and associated calcification 5.
• The expression of NLRP3 was significantly increased in serum and tissues of patients with PAD, and it was correlated with proinflammatory cytokine presence and macrophage accumulation 5.
• The activation of NLRP3 inflammasome may contribute to the development of peripheral neuropathy, and it may represent a potential therapeutic target for the treatment of this condition 1, 3.