Can cannabinoids be a potential therapeutic tool in amyotrophic lateral sclerosis?

Amyotrophic lateral sclerosis(ALS) is the most common degenerative disease of the motor neuron system. Over the last years, a growing interest was aimed to discovery new innovative and safer therapeutic approaches in the ALS treatment. In this context, the bioactive compounds of Cannabis sativa have shown antioxidant, anti-inflammatory and neuroprotective effects in preclinical models of central nervous system disease. However, most of the studies proving the ability of cannabinoids in delay disease progression and prolong survival in ALS were performed in animal model, whereas the few clinical trials that investigated cannabinoids-based medicines were focused only on the alleviation of ALS-related symptoms, not on the control of disease progression. The aim of this report was to provide a short but important overview of evidences that are useful to better characterize the efficacy as well as the molecular pathways modulated by cannabinoids.     

Understanding metabolic flexibility: a potential key to unlocking metabolic therapies in amyotrophic lateral sclerosis?

The role of metabolism in amyotrophic lateral sclerosis(ALS):ALS,is a predominantly sporadic,neurological disorder resulting in degeneration of both upper and lower motor neurons,resulting in the progressive failure of the neuromuscular system.The lifetime risk factor for developing ALS sits between 1 in 300 and 1 in 400.However,due to the speed of the disease course(2–3 years post-diagnosis)and the lack of effective therapies,ALS is still classified as a rare disease.     

New insights into serotonin 5-HT4 receptors : a novel therapeutic target for Alzheimer's disease?

The serotonin 5-HT4 receptor mediates many physiological effects in the central nervous system. The recent molecular identification of 5-HT4 receptors and the development of selective 5-HT4 receptor ligands have led to many important new insights into the signalling pathways and the physiological roles of these G protein-coupled-receptors in neurones. With respect to neurodegenerative disorders, it is suggested that 5-HT4 agonists may represent a new avenue for the treatment of Alzheimer's disease. This mini-review will focus on recent in vitro and in vivo pharmacological and biochemical studies showing the involvement of 5-HT4 receptors in cognitive processes and the amyloid precursor protein processing. The potential use of 5-HT4 agonists for the treatment of AD will be discussed.     

Mitochondrial quality control in amyotrophic lateral sclerosis:towards a common pathway?

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by loss of upper and lower motor neurons. Different mechanisms contribute to the disease initiation and progression, including mitochondrial dysfunction which has been proposed to be a central determinant in ALS patho-genesis. Indeed, while mitochondrial defects have been mainly described in ALS-linked SOD1 mutants, it is now well established that mitochondria become also dysfunctional in other ALS conditions. In such con-text, the mitochondrial quality control system allows to restore normal functioning of mitochondria and to prevent cell death, by both eliminating and replacing damaged mitochondrial components or by degrading the entire organelle through mitophagy. Recent evidence shows that ALS-related genes interfere with the mitochondrial quality control system. This review highlights how ineffective mitochondrial quality control may render motor neurons defenseless towards the accumulating mitochondrial damage in ALS.     

Prospects for bone marrow cell therapy in amyotrophic lateral sclerosis:how far are we from a clinical treatment?

Amyotrophic lateral sclerosis(ALS) is a fatal neurodegenerative disease that causes progressive muscular atrophy and death within 3–5 years after its onset.Despite the significant advances in knowledge of ALS pathology,no effective treatment is available.Therefore,it is imperative to search for new alternatives to treat ALS.Cell therapy,especially using bone-marrow cells,has showed to be very useful to protect the neural tissue in different brain disease or traumatic lesions.In ALS,most published results show beneficial effects of the use bone marrow cells,especially mesenchymal stromal cells.However,until now,the best outcome extends animal's lifespan by only a few weeks.It is essential to continue the search for a really effective therapy,testing different cells,routes and time-windows of administration.Studying the mechanisms that initiate and spread the degenerative process is also important to find out an effective therapy.Therefore,we discussed here some progresses that have been made using bone-marrow cell therapy as a therapeutic tool for ALS.