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Age-Related Midbrain Inflammation and Senescence in Parkinson's Disease

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Specialty Geriatrics
Date 2022 Jun 20
PMID 35721008
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Abstract

Immune responses are arising as a common feature of several neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), and Amyotrophic Lateral Sclerosis (ALS), but their role as either causative or consequential remains debated. It is evident that there is local inflammation in the midbrain in PD patients even before symptom onset, but the underlying mechanisms remain elusive. In this mini-review, we discuss this midbrain inflammation in the context of PD and argue that cellular senescence may be the cause for this immune response. We postulate that to unravel the relationship between inflammation and senescence in PD, it is crucial to first understand the potential causative roles of various cell types of the midbrain and determine how the possible paracrine spreading of senescence between them may lead to observed local immune responses. We hypothesize that secretion of pro-inflammatory factors by senescent cells in the midbrain triggers neuroinflammation resulting in immune cell-mediated killing of midbrain dopaminergic (DA) neurons in PD.

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References
1.
Trias E, Beilby P, Kovacs M, Ibarburu S, Varela V, Barreto-Nunez R . Emergence of Microglia Bearing Senescence Markers During Paralysis Progression in a Rat Model of Inherited ALS. Front Aging Neurosci. 2019; 11:42. PMC: 6403180. DOI: 10.3389/fnagi.2019.00042. View

2.
Liu Z, Zhai X, Du Z, Xu F, Huang Y, Wang X . Dopamine receptor D2 on CD4 T cells is protective against neuroinflammation and neurodegeneration in a mouse model of Parkinson's disease. Brain Behav Immun. 2021; 98:110-121. DOI: 10.1016/j.bbi.2021.08.220. View

3.
Grozdanov V, Bousset L, Hoffmeister M, Bliederhaeuser C, Meier C, Madiona K . Increased Immune Activation by Pathologic α-Synuclein in Parkinson's Disease. Ann Neurol. 2019; 86(4):593-606. DOI: 10.1002/ana.25557. View

4.
Tasdemir N, Lowe S . Senescent cells spread the word: non-cell autonomous propagation of cellular senescence. EMBO J. 2013; 32(14):1975-6. PMC: 3715860. DOI: 10.1038/emboj.2013.139. View

5.
Baird J, Bourdette D, Meshul C, Quinn J . The key role of T cells in Parkinson's disease pathogenesis and therapy. Parkinsonism Relat Disord. 2018; 60:25-31. DOI: 10.1016/j.parkreldis.2018.10.029. View