Glia and alpha-synuclein in neurodegeneration: A complex interaction

Area of Science:

• Neuroscience
• Pathology
• Cell Biology

Background:

• α-Synucleinopathies (ASP) are adult-onset neurodegenerative disorders including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA).
• These diseases are defined by α-synuclein (AS) aggregates in neurons and/or glia.
• While PD and DLB show neuronal Lewy bodies (LB), MSA is characterized by glial cytoplasmic inclusions (GCIs).

Purpose of the Study:

• To review the role of glial cells in α-synucleinopathies.
• To highlight AS-dependent alterations in glial function.
• To elucidate the impact of glial dysfunction on neuronal vulnerability.

Main Methods:

• Literature review of studies on α-synucleinopathies.
• Analysis of glial cell involvement in PD, DLB, and MSA pathogenesis.
• Examination of AS aggregate effects on glial and neuronal cells.

Main Results:

• Glial AS-inclusions can lead to reduced trophic support and neuronal loss.
• Microgliosis and astrogliosis are prevalent in ASP brains and contribute to disease progression.
• Altered glial function significantly impacts neuronal vulnerability in ASP.

Conclusions:

• Glia play a multifaceted role in the initiation and progression of α-synucleinopathies.
• Understanding glial contributions is crucial for developing therapeutic strategies for ASP.
• Targeting glial dysfunction may offer a novel approach to treating neurodegenerative diseases like PD, DLB, and MSA.