Inflammation As Common Link to Progressive Neurological Diseases

Overview

Journal Arch Toxicol

Specialty Toxicology

Date 2023 Nov 14

PMID 37964100

Authors

Ana Dias-Carvalho

Susana Isabel Sa

Felix Carvalho

Eduarda Fernandes

Vera Marisa Costa

Affiliations

Soon will be listed here.

Abstract

Life expectancy has increased immensely over the past decades, bringing new challenges to the health systems as advanced age increases the predisposition for many diseases. One of those is the burden of neurologic disorders. While many hypotheses have been placed to explain aging mechanisms, it has been widely accepted that the increasing pro-inflammatory status with advanced age or "inflammaging" is a main determinant of biological aging. Furthermore, inflammaging is at the cornerstone of many age-related diseases and its involvement in neurologic disorders is an exciting hypothesis. Indeed, aging and neurologic disorders development in the elderly seem to share some basic pathways that fundamentally converge on inflammation. Peripheral inflammation significantly influences brain function and contributes to the development of neurological disorders, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Understanding the role of inflammation in the pathogenesis of progressive neurological diseases is of crucial importance for developing effective treatments and interventions that can slow down or prevent disease progression, therefore, decreasing its social and economic burden.

Citing Articles

JNK inhibition mitigates sepsis-associated encephalopathy via attenuation of neuroinflammation, oxidative stress and apoptosis.

Gagnani R, Singh H, Suri M, Bali A Metab Brain Dis. 2025; 40(3):148.

PMID: 40080264 DOI: 10.1007/s11011-025-01563-4.

Targeting Cytokine-Mediated Inflammation in Brain Disorders: Developing New Treatment Strategies.

Mallick R, Basak S, Chowdhury P, Bhowmik P, Das R, Banerjee A Pharmaceuticals (Basel). 2025; 18(1).

PMID: 39861166 PMC: 11769149. DOI: 10.3390/ph18010104.

The Interplay Between Accumulation of Amyloid-Beta and Tau Proteins, PANoptosis, and Inflammation in Alzheimer's Disease.

Zhuang X, Lin J, Song Y, Ban R, Zhao X, Xia Z Neuromolecular Med. 2025; 27(1):2.

PMID: 39751702 DOI: 10.1007/s12017-024-08815-z.

Should We Consider Neurodegeneration by Itself or in a Triangulation with Neuroinflammation and Demyelination? The Example of Multiple Sclerosis and Beyond.

Perdaens O, van Pesch V Int J Mol Sci. 2024; 25(23.

PMID: 39684351 PMC: 11641818. DOI: 10.3390/ijms252312637.

A transient blood IL-17 increase triggers neuroinflammation in cerebellum and motor incoordination in hyperammonemic rats.

Arenas Y, Montoliu C, Llansola M, Felipo V J Neuroinflammation. 2024; 21(1):314.

PMID: 39616376 PMC: 11608494. DOI: 10.1186/s12974-024-03310-5.

References

Voskuhl R, Patel K, Paul F, Gold S, Scheel M, Kuchling J . Sex differences in brain atrophy in multiple sclerosis. Biol Sex Differ. 2020; 11(1):49. PMC: 7456053. DOI: 10.1186/s13293-020-00326-3. View

Szekely C, Green R, Breitner J, Ostbye T, Beiser A, Corrada M . No advantage of A beta 42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies. Neurology. 2008; 70(24):2291-8. PMC: 2755238. DOI: 10.1212/01.wnl.0000313933.17796.f6. View

Salou M, Nicol B, Garcia A, Laplaud D . Involvement of CD8(+) T Cells in Multiple Sclerosis. Front Immunol. 2015; 6:604. PMC: 4659893. DOI: 10.3389/fimmu.2015.00604. View

Scalzo P, Kummer A, Cardoso F, Teixeira A . Increased serum levels of soluble tumor necrosis factor-alpha receptor-1 in patients with Parkinson's disease. J Neuroimmunol. 2009; 216(1-2):122-5. DOI: 10.1016/j.jneuroim.2009.08.001. View

Li Y, Yang Y, Zhao A, Luo N, Niu M, Kang W . Parkinson's disease peripheral immune biomarker profile: a multicentre, cross-sectional and longitudinal study. J Neuroinflammation. 2022; 19(1):116. PMC: 9131564. DOI: 10.1186/s12974-022-02481-3. View

Hansen-Kyle L . A concept analysis of healthy aging. Nurs Forum. 2005; 40(2):45-57. DOI: 10.1111/j.1744-6198.2005.00009.x. View

Wang R, Reddy P . Role of Glutamate and NMDA Receptors in Alzheimer's Disease. J Alzheimers Dis. 2016; 57(4):1041-1048. PMC: 5791143. DOI: 10.3233/JAD-160763. View

Mucke L, Masliah E, Yu G, Mallory M, Rockenstein E, Tatsuno G . High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci. 2000; 20(11):4050-8. PMC: 6772621. View

Seif F, Khoshmirsafa M, Aazami H, Mohsenzadegan M, Sedighi G, Bahar M . The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells. Cell Commun Signal. 2017; 15(1):23. PMC: 5480189. DOI: 10.1186/s12964-017-0177-y. View

10.

Santoro A, Spinelli C, Martucciello S, Nori S, Capunzo M, Puca A . Innate immunity and cellular senescence: The good and the bad in the developmental and aged brain. J Leukoc Biol. 2018; 103(3):509-524. DOI: 10.1002/JLB.3MR0118-003R. View

11.

Shigemori K, Nomura S, Umeda T, Takeda S, Tomiyama T . Peripheral Aβ acts as a negative modulator of insulin secretion. Proc Natl Acad Sci U S A. 2022; 119(12):e2117723119. PMC: 8944757. DOI: 10.1073/pnas.2117723119. View

12.

McKinnon C, de Snoo M, Gondard E, Neudorfer C, Chau H, Ngana S . Early-onset impairment of the ubiquitin-proteasome system in dopaminergic neurons caused by α-synuclein. Acta Neuropathol Commun. 2020; 8(1):17. PMC: 7023783. DOI: 10.1186/s40478-020-0894-0. View

13.

Tian L, Rauvala H, Gahmberg C . Neuronal regulation of immune responses in the central nervous system. Trends Immunol. 2009; 30(2):91-9. DOI: 10.1016/j.it.2008.11.002. View

14.

Albayram M, Smith G, Tufan F, Tuna I, Bostanciklioglu M, Zile M . Non-invasive MR imaging of human brain lymphatic networks with connections to cervical lymph nodes. Nat Commun. 2022; 13(1):203. PMC: 8752739. DOI: 10.1038/s41467-021-27887-0. View

15.

Fukuyama R, Izumoto T, Fushiki S . The cerebrospinal fluid level of glial fibrillary acidic protein is increased in cerebrospinal fluid from Alzheimer's disease patients and correlates with severity of dementia. Eur Neurol. 2001; 46(1):35-8. DOI: 10.1159/000050753. View

16.

Qin H, Buckley J, Li X, Liu Y, Fox 3rd T, Meares G . Inhibition of the JAK/STAT Pathway Protects Against α-Synuclein-Induced Neuroinflammation and Dopaminergic Neurodegeneration. J Neurosci. 2016; 36(18):5144-59. PMC: 6123006. DOI: 10.1523/JNEUROSCI.4658-15.2016. View

17.

Verberk I, Laarhuis M, van den Bosch K, Ebenau J, van Leeuwenstijn M, Prins N . Serum markers glial fibrillary acidic protein and neurofilament light for prognosis and monitoring in cognitively normal older people: a prospective memory clinic-based cohort study. Lancet Healthy Longev. 2022; 2(2):e87-e95. DOI: 10.1016/S2666-7568(20)30061-1. View

18.

Kamma E, Lasisi W, Libner C, Ng H, Plemel J . Central nervous system macrophages in progressive multiple sclerosis: relationship to neurodegeneration and therapeutics. J Neuroinflammation. 2022; 19(1):45. PMC: 8830034. DOI: 10.1186/s12974-022-02408-y. View

19.

Liao Y, Wang B, Cheng H, Kuo L, Wolfe M . Tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma stimulate gamma-secretase-mediated cleavage of amyloid precursor protein through a JNK-dependent MAPK pathway. J Biol Chem. 2004; 279(47):49523-32. DOI: 10.1074/jbc.M402034200. View

20.

Chu J, Ji W, Zhuang J, Gong B, Chen X, Cheng W . Nanoparticles-based anti-aging treatment of Alzheimer's disease. Drug Deliv. 2022; 29(1):2100-2116. PMC: 9302016. DOI: 10.1080/10717544.2022.2094501. View