npj Parkinsons Dis: Parkinson's disease, the inflammasome facilitates the assessment of the condition

Parkinson's disease (PD) is a complex age-related neurodegenerative disorder affecting multiple systems and clinically characterized by a range of motor and non-motor symptoms
.

Diagnostic tests and neuroprotective strategies have been slow to emerge, in part because the molecular mechanisms underlying disease initiation and progression have not been fully defined

diagnosis

Figure 1 Title of the paper

Figure 1 Title of the paper

Neuroinflammation and loss of diencephalic dopaminergic neurons have been observed in postmortem tissue from Parkinson's disease patients, and it is widely believed that inflammation contributes to the progression of neurodegenerative processes
.

Evidence supporting a role for neuroinflammation in PD comes from animal models and epidemiological studies showing that the use of nonsteroidal anti-inflammatory drugs (NSAIDs), particularly ibuprofen, is associated with a reduced risk of developing PD
.

It is estimated that 30-70% of dopaminergic neurons have been lost by the time motor symptoms develop and PD is diagnosed
.

We must leverage our growing understanding of PD-related pathophysiology, such as inflammation, to help understand the complexity of PD and to inform the development of preventive measures and neuroprotective strategies to avoid onset or slow disease progression

prevention

Inflammasomes are proinflammatory intracellular complexes defined by proteins belonging to the nucleotide-binding domain-like receptors (NLRs), absent melanoma 2-like receptors (ALRs), or Pyrin pattern recognition receptor families
.

Assembly of the inflammasome complex drives caspase-1 catalysis, initiating cytokine maturation and secretion, and possibly febrile disease, an inflammatory subclass of programmed cell death

Inflammasomes are increasingly linked to neurodegenerative diseases, especially Alzheimer's disease and Parkinson's disease
.

This link is intuitive because NLRP3 inflammasome activity can be triggered by germ-free cellular stress associated with neurodegenerative disease pathology, including cell death, mitochondrial stress, reactive oxygen species (ROS), and proteinaceous damage, including amyloid -β and α-synuclein aggregation

Growing evidence links the NLRP3 inflammasome to PD, including a recent report describing the Nlrp3 inflammasome in response to fibrillar α-synuclein exposure, ROS production, and the occupational toxicant manganese; these three germ-free inflammatory triggers implicated in the development and pathophysiology of PD
.

In this way, Faith L Anderson of the Geisel School of Medicine at Dartmouth College in the United States and others explored the relationship between the inflammasome and PD
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They found:

The NLRP3 inflammasome is expressed in multiple cell types of the human diencephalon
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Figure 2 The correlation between NLR and PD pathological changes

Figure 2 The correlation between NLR and PD pathological changes

In addition, polymorphisms of NLRP3 were associated with a reduced risk of PD;

In addition, polymorphisms of NLRP3 were associated with a reduced risk of PD;

Inactivation of NLRP3 is neuroprotective in a toxicant-based mouse model of PD
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Inactivation of NLRP3 is neuroprotective in a toxicant-based mouse model of PD
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The significance of this study is the discovery that inactivation of the NLRP3 inflammasome may benefit PD patients
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The significance of this study is the discovery that inactivation of the NLRP3 inflammasome may benefit PD patients
.

Original source:
Anderson FL, von Herrmann KM, Andrew AS, et al.

Plasma-borne indicators of inflammasome activity in Parkinson's disease patients.
npj Parkinsons Dis.

Original source:
Anderson FL, von Herrmann KM, Andrew AS, et al.
Plasma-borne indicators of inflammasome activity in Parkinson's disease patients.
npj Parkinsons Dis.
2021;7(1):2.
doi:10.
1038/s41531-020-00147 -6 Plasma-borne indicators of inflammasome activity in Parkinson's disease patients.
npj Parkinsons Dis.
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