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Physiological and pathophysiological functions of NLRP6: pro- and anti-inflammatory roles.

ABSTRACT: The nucleotide-binding oligomerization and leucine-rich repeat receptor (NLR) protein family consists of important immune sensors that form inflammasomes, a cytosolic multi-protein platform that induces caspase-1 activation and is involved in different inflammatory pathologies. The NLR family pyrin domain containing 6 (NLRP6) is a receptor that can signal by forming inflammasomes, but which can also play an important role without forming inflammasomes. NLRP6 regulates intestinal homeostasis and inflammation, but also is involved in cancer, the nervous system or liver diseases, with both protective and deleterious consequences. In the present article, we review the different roles of NLRP6 in these processes and offer new insights into NLRP6 activation.

SUBMITTER: Angosto-Bazarra D

PROVIDER: S-EPMC9160023 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Physiological and pathophysiological functions of NLRP6: pro- and anti-inflammatory roles.

Angosto-Bazarra Diego D Molina-López Cristina C Pelegrín Pablo P

Communications biology 20220601 1

The nucleotide-binding oligomerization and leucine-rich repeat receptor (NLR) protein family consists of important immune sensors that form inflammasomes, a cytosolic multi-protein platform that induces caspase-1 activation and is involved in different inflammatory pathologies. The NLR family pyrin domain containing 6 (NLRP6) is a receptor that can signal by forming inflammasomes, but which can also play an important role without forming inflammasomes. NLRP6 regulates intestinal homeostasis and ...[more]

PMID: 35650327

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Project description:This review describes and summarizes the role of neuronal nitric oxide synthase (nNOS) on the central nervous system, particularly on brain regions such as the ventrolateral medulla (VLM) and the periaqueductal gray matter (PAG), and on blood vessels and the heart that are involved in the regulation and control of the cardiovascular system (CVS). Furthermore, we shall also review the functional aspects of nNOS during several physiological, pathophysiological, and clinical conditions such as exercise, pain, cerebral vascular accidents or stroke and hypertension. For example, during stroke, a cascade of molecular, neurochemical, and cellular changes occur that affect the nervous system as elicited by generation of free radicals and nitric oxide (NO) from vulnerable neurons, peroxide formation, superoxides, apoptosis, and the differential activation of three isoforms of nitric oxide synthases (NOSs), and can exert profound effects on the CVS. Neuronal NOS is one of the three isoforms of NOSs, the others being endothelial (eNOS) and inducible (iNOS) enzymes. Neuronal NOS is a critical homeostatic component of the CVS and plays an important role in regulation of different systems and disease process including nociception. The functional and physiological roles of NO and nNOS are described at the beginning of this review. We also elaborate the structure, gene, domain, and regulation of the nNOS protein. Both inhibitory and excitatory role of nNOS on the sympathetic autonomic nervous system (SANS) and parasympathetic autonomic nervous system (PANS) as mediated via different neurotransmitters/signal transduction processes will be explored, particularly its effects on the CVS. Because the VLM plays a crucial function in cardiovascular homeostatic mechanisms, the neuroanatomy and cardiovascular regulation of the VLM will be discussed in conjunction with the actions of nNOS. Thereafter, we shall discuss the up-to-date developments that are related to the interaction between nNOS and cardiovascular diseases such as hypertension and stroke. Finally, we shall focus on the role of nNOS, particularly within the PAG in cardiovascular regulation and neurotransmission during different types of pain stimulus. Overall, this review focuses on our current understanding of the nNOS protein, and provides further insights on how nNOS modulates, regulates, and controls cardiovascular function during both physiological activity such as exercise, and pathophysiological conditions such as stroke and hypertension.

Dataset Information

Physiological and pathophysiological functions of NLRP6: pro- and anti-inflammatory roles.

Publications

Physiological and pathophysiological functions of NLRP6: pro- and anti-inflammatory roles.

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