Modeling the neuroimmune system in Alzheimer's and Parkinson's diseases.

Parkinson's disease (PD) and Alzheimer's disease (AD) are neurodegenerative disorders caused by the interaction of genetic, environmental, and familial factors. These diseases have distinct pathologies and symptoms that are linked to specific cell populations in the brain. Notably, the immune system has been implicated in both diseases, with a particular focus on the dysfunction of microglia, the brain's resident immune cells, contributing to neuronal loss and exacerbating symptoms. Researchers use models of the neuroimmune system to gain a deeper understanding of the physiological and biological aspects of these neurodegenerative diseases and how they progress. Several in vitro and in vivo models, including 2D cultures and animal models, have been utilized. Recently, advancements have been made in optimizing these existing models and developing 3D models and organ-on-a-chip systems, holding tremendous promise in accurately mimicking the intricate intracellular environment. As a result, these models represent a crucial breakthrough in the transformation of current treatments for PD and AD by offering potential for conducting long-term disease-based modeling for therapeutic testing, reducing reliance on animal models, and significantly improving cell viability compared to conventional 2D models. The application of 3D and organ-on-a-chip models in neurodegenerative disease research marks a prosperous step forward, providing a more realistic representation of the complex interactions within the neuroimmune system. Ultimately, these refined models of the neuroimmune system aim to aid in the quest to combat and mitigate the impact of debilitating neuroimmune diseases on patients and their families.

Inflammation and Huntington's disease - a neglected therapeutic target?

INTRODUCTION: Huntington's Disease (HD) is a genetic neurodegenerative disease for which there is currently no disease-modifying treatment. One of several underlying mechanisms proposed to be involved in HD pathogenesis is inflammation; there is now accumulating evidence that the immune system may play an integral role in disease pathology and progression. As such, modulation of the immune system could be a potential therapeutic target for HD. AREAS COVERED: To date, the number of trials targeting immune aspects of HD has been limited. However, targeting it, may have great advantages over other therapeutic areas, given that many drugs already exist that have actions in this system coupled to the fact that inflammation can be measured both peripherally and, to some extent, centrally using CSF and PET imaging. In this review, we look at evidence that the immune system and the newly emerging area of the microbiome are altered in HD patients, and then present and discuss clinical trials that have targeted different parts of the immune system. EXPERT OPINION: We then conclude by discussing how this field might develop going forward, focusing on the role of imaging and other biomarkers to monitor central immune activation and response to novel treatments in HD.

The role of DNA damage response in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rapidly disabling and fatal neurodegenerative disease. Due to insufficient disease-modifying treatments, there is an unmet and urgent need for elucidating disease mechanisms that occur early and represent common triggers in both familial and sporadic ALS. Emerging evidence suggests that impaired DNA damage response contributes to age-related somatic accumulation of genomic instability and can trigger or accelerate ALS pathological manifestations. In this review, we summarize and discuss recent studies indicating a direct link between DNA damage response and ALS. Further mechanistic understanding of the role genomic instability is playing in ALS disease pathophysiology will be critical for discovering new therapeutic avenues.