Inflammasome assembly in neurodegenerative diseases
Open accessAbstract
Neurodegenerative disorders are characterized by the progressive dysfunction and death of selectively vulnerable neuronal populations, often associated with the accumulation of aggregated host proteins. Sustained brain inflammation and hyperactivation of inflammasome complexes have been increasingly demonstrated to contribute to neurodegenerative disease progression. Here, we review molecular mechanisms leading to inflammasome assembly in neurodegeneration. We focus primarily on four degenerative brain disorders in which inflammasome hyperactivation has been well documented: Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and the spectrum of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We discuss shared and divergent principles of inflammasome assembly across these disorders, and underscore the differences between neurodegeneration-associated inflammasome activation pathways and their peripheral-immune counterparts. We examine how aberrant assembly of inflammasome complexes may amplify pathology in neurodegeneration, including misfolded protein aggregation, and highlight prospects for neurotherapeutic interventions based on targeting inflammasome pathways.
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Exosomes act as vehicles for intercellular transfer of Aβ, tau, and inflammatory mediators between neurons, astrocytes, and microglia, facilitating spread of pathology.
“Moreover, crosstalk between inflammasomes and exosomes introduces an additional regulatory dimension, whereby exosomes act as vehicles for the intercellular transfer of Aβ, tau, and inflammatory mediators between neurons, astrocytes, and microglia, thereby facilitating the spread of pathology (Fig. 6).”
From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [91]
The passages on tau pathology and microglia–astrocyte crosstalk (indexed as Abstract; page unavailable) describe inflammasome effects, including transfer of fragmented mitochondria, but not exosome-mediated transfer of Aβ, tau, or inflammatory mediators. Searches for “exosomes” and “extracellular vesicles” found no passage addressing the claimed mechanism. (LLM, conf=0.75)
Experimental — accuracy not yet measuredInflammasome activation enhances exosome release, while exosomes themselves can trigger inflammasome activity.
“Conversely, inflammasome activation enhances exosome release, while exosomes themselves can trigger inflammasome activity [91].”
From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [91]
The paper’s overview and its discussion of inflammasome crosstalk with cell-death pathways (both labeled Abstract in our copy; no page given) do not address exosomes. Searches for “exosome,” “exosome release inflammasome activation,” and “exosomes extracellular vesicles secretion NLRP3” found no passage supporting either direction of the claimed relationship. (LLM, conf=0.73)
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- Authors
- Singh, J., Habean, M. L., & Panicker, N.
- Affiliations
- Cleveland Clinic (US)
- Corresponding author
- Panicker, Nikhil
- Venue
- Trends in Neurosciences
- Publisher
- Elsevier BV
- Published
- 2023-10
- Volume
- 46
- Issue
- 10
- Pages
- 814-831
- ISSN
- 0166-2236 (ISSN-L)
- PMC
- PMC10530301
- OpenAlex
- W4386122874
- Cited by
- 83
- References
- 35
- Citations by year
- 2026: 25 · 2025: 27 · 2024: 29 · 2023: 2
- FWCI
- 2.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 354 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Trends in Neurosciences (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Congressionally Directed Medical Research Programs (PD220039)
- National Institutes of Health
- U.S. Department of Defense
- National Institute on Aging (R00AG066862)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- inflammasome assembly, neurodegenerative diseases, neuroinflammation, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, frontotemporal dementia, protein aggregation, inflammasome-targeted therapy
- MeSH terms
- Alzheimer Disease, Amyotrophic Lateral Sclerosis, Humans, Parkinson Disease, Neurodegenerative Diseases, Inflammasomes
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