Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to significant motor and non-motor symptoms. Recent research highlights the critical role of microglia, the resident immune cells of the central nervous system, in the pathogenesis and progression of PD. Microglia contribute to neuroinflammation through the release of pro-inflammatory cytokines and reactive oxygen species, exacerbating neuronal damage. Moreover, α-synuclein aggregates, a hallmark of PD, activate microglia, further promoting inflammation and neurodegeneration. This review explores the dual role of microglia in PD, encompassing both their neuroprotective functions and their contribution to neuroinflammation. We discuss the molecular mechanisms underlying microglial activation and their interactions with astrocytes, another crucial glial cell type. The review also examines potential therapeutic targets aimed at modulating microglial activity to mitigate neuroinflammation and slow the progression of PD. Current therapeutic strategies predominantly focus on symptomatic relief through dopaminergic medications. However, emerging therapies targeting microglial activation, such as anti-inflammatory drugs, immunomodulators, and novel agents like metabotropic glutamate receptor 5 (mGluR5) modulators, offer promising avenues for disease modification. Understanding the complex interplay between microglia and other cellular components in the PD brain is essential for developing effective treatments that address the underlying pathophysiological mechanisms of the disease.
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Maria Victória Rocha Fontenele Maia ,
Victor Hugo Melo Freitas,
Lara Oliveira da Nóbrega ,
Lucas Olímpio Coimbra ,
Aline Moreira Lócio,
Fairane Sousa Duarte,
Rodrigo Mariano Ribeiro,
Victor Monteiro Mororó,
Sara Diógenes Peixoto de Medeiros ,
Amanda Rebouças Bezerra de Menezes ,
Rafaella Iughetti da Costa,
Luciano Barroso de Albuquerque-Filho,
Lara Maria Fujita Vieira Lima,
Camilla Costa Sallem,
Camilla Teixeira Pinheiro Gusmão,
Yuri Borges Morais,
Luiz da Silva Aldir,
Tiago Antoniol,
Isaac Dantas Sales Pimentel,
Natalia Marinho Porto Lima ,
Júlio César Claudino dos Santos,
Beyond behavioral changes in semantic dementia: principal hurdles on the road to the clinic
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Brazilian Journal of Clinical Medicine and Review: Vol. 1 No. 3 (2023): July/September - 2023