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Role of TREM2 in Alzheimer’s Disease: A Long Road Ahead

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Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by an increasing deterioration of memory, which is concomitant with additional cognitive deficits. Neurofibrillary tangles and senile plaques are two pivotal proteins inside the brain that are considered essential to obstruct the normal cognitive function of the brain. Genetic variations in TREM2 gene disturb the neuroinflammatory action of microglia in reducing the progression of the disease.

TREM2 is a transmembrane receptor present on the microglia, which has an important function in neuroinflammation. Genome-wide association studies identified variants of TREM2 gene and linked it with the risk of developing AD, by 2–4 folds. Numerous studies on mice models have revealed the relationship between mutations of TREM2 gene and its effect on amyloid burden and tau pathology in the brain that gets affected by AD. This review summarizes the role of TREM2 and its variants in the progression of AD and tries to delve deep into the role of soluble TREM2 as an effective biomarker and impending neuroprotection in AD. It also focuses on the strategies to develop therapeutic agents against TREM2 by employing its expression, function, and signalling pathways. The current challenges posed against prospective therapy for AD are also discussed.

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Authors and Affiliations

  1. Poona College of Pharmacy, Bharati Vidyapeeth (Deemed To Be University) Erandawane, Pune, 411038, Maharashtra, India

    Bhargavi Kulkarni & Dileep Kumar

  2. Faculty of Medicine, University of Porto (FMUP), Alameda Prof. Hernani Monteiro, 4200-319, Porto, Portugal

    Natália Cruz-Martins

  3. Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal

    Natália Cruz-Martins

  4. Institute of Research and Advanced, Training in Health Sciences and Technologies (CESPU), Rua Central de Gandra, 1317,, 4585-116, Gandra, PRD, Portugal

    Natália Cruz-Martins

  5. Karpagam College of Pharmacy, Coimbatore, 641032, Tamil Nadu, India

    Satheeshkumar Sellamuthu

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  1. Bhargavi Kulkarni
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  4. Satheeshkumar Sellamuthu
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Kulkarni, B., Kumar, D., Cruz-Martins, N. et al. Role of TREM2 in Alzheimer’s Disease: A Long Road Ahead. Mol Neurobiol 58, 5239–5252 (2021). https://doi.org/10.1007/s12035-021-02477-9

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