Synthesis and biological evaluation of a new class of benzothiazines as neuroprotective agents.

Neurodegenerative diseases are disorders related to the degeneration of central neurons that gradually lead to various, severe alterations of cognitive and/or motor functions. Currently, for no such diseases does any pharmacological treatment exist able to arrest its progression. Riluzole (1) is a small molecule able to interfere with multiple cellular and molecular mechanisms of neurodegeneration, and is the only approved treatment of amyotrophic lateral sclerosis (ALS), the progression of which proved to significantly slow, thus increasing somewhat average survival.

Progesterone and its derivatives are neuroprotective agents in experimental diabetic neuropathy: a multimodal analysis.

One important complication of diabetes is damage to the peripheral nervous system. However, in spite of the number of studies on human and experimental diabetic neuropathy, the current therapeutic arsenal is meagre. Consequently, the search for substances to protect the nervous system from the degenerative effects of diabetes has high priority in biomedical research.

Neuroactive steroids: A therapeutic approach to maintain peripheral nerve integrity during neurodegenerative events.

It is now well known that peripheral nerves are a target for the action of neuroactive steroids. This review summarizes observations obtained so far, indicating that through the interaction with classical and nonclassical steroid receptors, neuroactive steroids (e.g.

Neuroactive steroids prevent peripheral myelin alterations induced by diabetes.

The effect of the neuroactive steroids progesterone, dihydroprogesterone and tetrahydroprogesterone on myelin abnormalities induced by diabetes was studied in the sciatic nerve of adult male rats treated with streptozotocin. Streptozotocin increased blood glucose levels and decreased body weight gain, parameters not affected by steroids. Streptozotocin increased the number of fibers with myelin infoldings in the axoplasm, 8 months after the treatment.

Ro5-4864, a synthetic ligand of peripheral benzodiazepine receptor, reduces aging-associated myelin degeneration in the sciatic nerve of male rats.

The peripheral-type benzodiazepine receptor (PBR) is a protein predominantly located in the mitochondrial outer membrane that plays an important role in the regulation of cell survival and proliferation. Previous studies have shown an enhanced expression of PBR in the regenerating sciatic nerve, suggesting that this protein may be involved in the regenerative response. The rat sciatic nerve suffers important structural alterations with aging, including alterations in the morphology of myelin sheaths and a decrease in the number of myelinated fibers.