The search for new therapies to reduce symptoms and find a cure for Parkinson’s disease has focused attention on two key points: the accumulation of alpha-synuclein aggregates and astrocytes. The former is a hallmark of the disease, while the latter corresponds to a type of glial cell with an important role in both the prevention and development of this neurodegenerative disorder. Traditionally, research has focused on therapies targeting dopaminergic neurons. Currently, as more is known about the genetic and molecular factors and the neuroglial interaction in the disease, great emphasis has been placed on the neuroprotective role of astrocytes in the early stages of the disease and on the astrocytic capture of alpha-synuclein under both physiological and pathological conditions. This review aims to analyze the contribution of alpha-synuclein and astrocytes to the development and progression of Parkinson’s disease, as well as to evaluate recent therapeutic proposals specifically focused on synucleopathies and astroglial cells as potential therapies for the disease.

Astrocyte activation is a critical aspect of brain health and disease, and the central circadian clock protein BMAL1 has emerged as a regulator of astrogliosis and inflammatory gene expression. Bmal1 deletion in astrocytes reprograms endolysosomal transcriptional pathways, inducing endocytosis, lysosomal degradation, and autophagic activity. This regulation of proteostasis by BMAL1 implicates circadian clock proteins in neurodegenerative diseases. Studies suggest that astrocyte activation is a complex process with diverse phenotypes beyond classic markers such as GFAP, exhibiting neurotoxic and neuroprotective effects. Deletion of Bmal1 in astrocytes has shown protective effects in models of Alzheimer’s disease (AD) and Parkinson’s disease (PD), influencing Aβ accumulation and α-syn pathology, respectively, through a state of protective astrocyte activation that mitigates tauopathy and α-syn pathology, possibly through the induction of the chaperone protein BAG3. These findings suggest that BMAL1 is crucial in regulating astrocytic function and neuroprotection in neurodegenerative diseases. This review explores the relationship between circadian dysfunction and the development/progression of AD and PD. Furthermore, it recapitulates the most recent findings on manipulating the clock protein BMAL1 and its potential protective effects in astrocytes.