Identification of the abnormalities in astrocytic functions as potential drug targets for neurodegenerative disease.

INTRODUCTION: Historically, astrocytes were seen primarily as a supportive cell population within the brain; with neurodegenerative disease research focusing exclusively on malfunctioning neurons. However, astrocytes perform numerous tasks that are essential for maintenance of the central nervous system`s complex processes. Disruption of these functions can have negative consequences; hence, it is unsurprising to observe a growing amount of evidence for the essential role of astrocytes in the development and progression of neurodegenerative diseases. Targeting astrocytic functions may serve as a potential disease-modifying drug therapy in the future. AREAS COVERED: The present review emphasizes the key astrocytic functions associated with neurodegenerative diseases and explores the possibility of pharmaceutical interventions to modify these processes. In addition, the authors provide an overview of current advancement in this field by including studies of possible drug candidates. EXPERT OPINION: Glial research has experienced a significant renaissance in the last quarter-century. Understanding how disease pathologies modify or are caused by astrocyte functions is crucial when developing treatments for brain diseases. Future research will focus on building advanced models that can more precisely correlate to the state in the human brain, with the goal of routinely testing therapies in these models.

Cellular Models of Alpha-Synuclein Aggregation: What Have We Learned and Implications for Future Study.

Alpha-synuclein's role in diseases termed "synucleinopathies", including Parkinson's disease, has been well-documented. However, after over 25 years of research, we still do not fully understand the alpha-synuclein protein and its role in disease. In vitro cellular models are some of the most powerful tools that researchers have at their disposal to understand protein function. Advantages include good control over experimental conditions, the possibility for high throughput, and fewer ethical issues when compared to animal models or the attainment of human samples. On the flip side, their major disadvantages are their questionable relevance and lack of a "whole-brain" environment when it comes to modeling human diseases, such as is the case of neurodegenerative disorders. Although now, with the advent of pluripotent stem cells and the ability to create minibrains in a dish, this is changing. With this review, we aim to wade through the recent alpha-synuclein literature to discuss how different cell culture setups (immortalized cell lines, primary neurons, human induced pluripotent stem cells (hiPSCs), blood-brain barrier models, and brain organoids) can help us understand aggregation pathology in Parkinson's and other synucleinopathies.