TREM 2 in Parkinson’s Disease: A Promising Candidate Gene for Disease Susceptibility and Progression

<b>Background/Objectives</b>: The activation of microglia and the activity of innate immunity have recently been recognized as part of Parkinson’s Disease (PD) pathophysiology. Triggering receptor expressed on myeloid cells 2 (TREM2) is a gene with neuroprotective roles. Its variations a...

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Main Authors: Paolo Alonge, Carmela Rita Balistreri, Angelo Torrente, Daniele Magro, Elisa Rubino, Roberto Monastero
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Brain Sciences
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Online Access:https://www.mdpi.com/2076-3425/15/4/379
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author Paolo Alonge
Carmela Rita Balistreri
Angelo Torrente
Daniele Magro
Elisa Rubino
Roberto Monastero
author_facet Paolo Alonge
Carmela Rita Balistreri
Angelo Torrente
Daniele Magro
Elisa Rubino
Roberto Monastero
author_sort Paolo Alonge
collection DOAJ
description <b>Background/Objectives</b>: The activation of microglia and the activity of innate immunity have recently been recognized as part of Parkinson’s Disease (PD) pathophysiology. Triggering receptor expressed on myeloid cells 2 (TREM2) is a gene with neuroprotective roles. Its variations are associated with microglial-associated neurodegeneration. The objective of the present review is to investigate the current evidence on the role of TREM2 in PD pathophysiology. <b>Methods</b>: A comprehensive search was performed using PubMed, Medline, and Web of Science, looking for English papers investigating the role of TREM2 in PD, or more in general, the genetic profile of microglia. <b>Results</b>: Thirty-one papers were considered relevant. Preclinical studies with PD models showed some contradictory results, even if a loss of function of TREM2 is generally associated with a microglial activation in α-synuclein-induced inflammatory processes. The role for TREM2 genetic variations in PD patients should be taken with even more caution. The increase in the soluble extracellular segment of TREM2 (sTREM2) in cerebrospinal fluid of PD patients seems to be associated with increased risk of cognitive decline. <b>Conclusions</b>: There is increasing evidence that TREM2 may have an important role in PD pathophysiology as demonstrated by preclinical and clinical studies. Further investigations are needed to confirm this role and may lead the way for future targeted therapies for different neurodegenerative disorders.
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spelling doaj-art-cc4e14e79de646cda5c203734821dcec2025-08-20T03:14:23ZengMDPI AGBrain Sciences2076-34252025-04-0115437910.3390/brainsci15040379TREM 2 in Parkinson’s Disease: A Promising Candidate Gene for Disease Susceptibility and ProgressionPaolo Alonge0Carmela Rita Balistreri1Angelo Torrente2Daniele Magro3Elisa Rubino4Roberto Monastero5Memory and Parkinson’s Disease Center, Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University of Palermo, Via La Loggia 1, 90129 Palermo, ItalyCellular and Molecular Laboratory, Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University of Palermo, 90134 Palermo, ItalyMemory and Parkinson’s Disease Center, Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University of Palermo, Via La Loggia 1, 90129 Palermo, ItalyCellular and Molecular Laboratory, Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University of Palermo, 90134 Palermo, ItalyMemory and Parkinson’s Disease Center, Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University of Palermo, Via La Loggia 1, 90129 Palermo, ItalyMemory and Parkinson’s Disease Center, Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University of Palermo, Via La Loggia 1, 90129 Palermo, Italy<b>Background/Objectives</b>: The activation of microglia and the activity of innate immunity have recently been recognized as part of Parkinson’s Disease (PD) pathophysiology. Triggering receptor expressed on myeloid cells 2 (TREM2) is a gene with neuroprotective roles. Its variations are associated with microglial-associated neurodegeneration. The objective of the present review is to investigate the current evidence on the role of TREM2 in PD pathophysiology. <b>Methods</b>: A comprehensive search was performed using PubMed, Medline, and Web of Science, looking for English papers investigating the role of TREM2 in PD, or more in general, the genetic profile of microglia. <b>Results</b>: Thirty-one papers were considered relevant. Preclinical studies with PD models showed some contradictory results, even if a loss of function of TREM2 is generally associated with a microglial activation in α-synuclein-induced inflammatory processes. The role for TREM2 genetic variations in PD patients should be taken with even more caution. The increase in the soluble extracellular segment of TREM2 (sTREM2) in cerebrospinal fluid of PD patients seems to be associated with increased risk of cognitive decline. <b>Conclusions</b>: There is increasing evidence that TREM2 may have an important role in PD pathophysiology as demonstrated by preclinical and clinical studies. Further investigations are needed to confirm this role and may lead the way for future targeted therapies for different neurodegenerative disorders.https://www.mdpi.com/2076-3425/15/4/379TREM2PDParkinson’s diseaseneuroinflammationmicroglianeurodegenerative disorders
spellingShingle Paolo Alonge
Carmela Rita Balistreri
Angelo Torrente
Daniele Magro
Elisa Rubino
Roberto Monastero
TREM 2 in Parkinson’s Disease: A Promising Candidate Gene for Disease Susceptibility and Progression
Brain Sciences
TREM2
PD
Parkinson’s disease
neuroinflammation
microglia
neurodegenerative disorders
title TREM 2 in Parkinson’s Disease: A Promising Candidate Gene for Disease Susceptibility and Progression
title_full TREM 2 in Parkinson’s Disease: A Promising Candidate Gene for Disease Susceptibility and Progression
title_fullStr TREM 2 in Parkinson’s Disease: A Promising Candidate Gene for Disease Susceptibility and Progression
title_full_unstemmed TREM 2 in Parkinson’s Disease: A Promising Candidate Gene for Disease Susceptibility and Progression
title_short TREM 2 in Parkinson’s Disease: A Promising Candidate Gene for Disease Susceptibility and Progression
title_sort trem 2 in parkinson s disease a promising candidate gene for disease susceptibility and progression
topic TREM2
PD
Parkinson’s disease
neuroinflammation
microglia
neurodegenerative disorders
url https://www.mdpi.com/2076-3425/15/4/379
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