Aging is the most important risk factor for Parkinson’s disease (PD), a neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra pars compacta. Microglia, the resident immune cells of the brain, play a crucial role in neuroinflammation, which can be defined as an immune response taking place in the central nervous system. While neuroinflammation is not inherently detrimental for brain health, a chronic and uncontrolled neuroinflammatory activity is tightly associated with neuronal damage and neurodegenerative diseases, including PD. In this context, it is important to assess the impact of aging on microglial function and neuroinflammation, as microglial aging could increase PD onset risk through both gain- and loss-of-function mechanisms. This chapter examines the molecular mechanisms underlying microglial aging, including transcriptomic changes and altered signaling pathways that result in dysregulated cytokine production and impaired phagocytosis. These alterations exacerbate α-synuclein aggregation and spreading, which are central to PD pathology. Understanding the relationship between microglial aging, neuroinflammation, and neurodegeneration is crucial for identifying potential therapeutic targets to mitigate the effects of PD.
Involvement of microglial aging in neurodegenerative diseases: a focus on Parkinson’s disease
Kaur G.;Bubacco L.;Civiero L.;Greggio E.
2026
Abstract
Aging is the most important risk factor for Parkinson’s disease (PD), a neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra pars compacta. Microglia, the resident immune cells of the brain, play a crucial role in neuroinflammation, which can be defined as an immune response taking place in the central nervous system. While neuroinflammation is not inherently detrimental for brain health, a chronic and uncontrolled neuroinflammatory activity is tightly associated with neuronal damage and neurodegenerative diseases, including PD. In this context, it is important to assess the impact of aging on microglial function and neuroinflammation, as microglial aging could increase PD onset risk through both gain- and loss-of-function mechanisms. This chapter examines the molecular mechanisms underlying microglial aging, including transcriptomic changes and altered signaling pathways that result in dysregulated cytokine production and impaired phagocytosis. These alterations exacerbate α-synuclein aggregation and spreading, which are central to PD pathology. Understanding the relationship between microglial aging, neuroinflammation, and neurodegeneration is crucial for identifying potential therapeutic targets to mitigate the effects of PD.
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