Complementary strategies to be used in conjunction with animal models for multiple sclerosis drug discovery: adapting preclinical validation of drug candidates to the need of remyelinating strategies.

Introduction: The quest for novel MS therapies focuses on promoting remyelination and neuroprotection, necessitating innovative drug design paradigms and robust preclinical validation methods to ensure efficient clinical translation. The complexity of new drugs action mechanisms is strengthening the need for solid biological validation attempting to address all possible pitfalls and biases precluding access to efficient and safe drugs.

Areas Covered: In this review, the authors describe the different in vitro and in vivo models that should be used to create an integrated approach for preclinical validation of novel drugs, including the evaluation of the action mechanism.

Fluorinated apelin-13 mediates neuroprotective effects in multiple sclerosis models.

Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease leading to demyelination and axonal loss. Current treatments are immunomodulatory or immunosuppressive drugs acting on the inflammatory component. However, these treatments do not adequately address the crucial aspect of neuroprotection.

Implication of the Transmembrane Domain in the Interleukin 10 Receptor Platform Oligomerisation.

Interleukin 10 (IL-10) exerts anti-inflammatory and immune regulatory roles through its fixation to the IL-10 receptor (IL-10R). The two subunits (IL-10Rα and IL-10Rβ) organise themselves to form a hetero-tetramer to induce the activation of the transcription factor STAT3. We analysed the activation patterns of the IL-10R, especially the contribution of the transmembrane (TM) domain of the IL-10Rα and IL-10Rβ subunits, as evidence accumulates that this short domain has tremendous implications in receptor oligomerisation and activation.