Studio dell'effetto di piante medicinali endemiche del Marocco sui processi infiammatori cerebrali indotti da radicali liberi

Responsabili di progetto

Anna Moroni, Taoufiq Fechtali

Accordo

MAROCCO - CNRST - Centre National pour la Recherche Scientifique et Technique

Bando

CNR/CNRST 2014-2015

Dipartimento

Scienze fisiche e tecnologie della materia

Area tematica

Scienze fisiche e tecnologie della materia

Stato del progetto

Nuovo

Proposta di ricerca

Background:
Each country and continent face myriads of health and environmental problems, some of which are unique, but some are coming up as an issue with the advent of modern technology, new industry and global integration. Environmental pollution is one such issue that has already cropped up as a chronic problem in developed nations; but it is becoming a major and acute issue of concern in developing nations. Human and animal health as well as the ecological ramifications of globalization provides an opportunity to find solutions to these incipient environment-related problems that are slowly looming in developing nations like Morocco.
The proposed study therefore allows careful evaluation of the measures and steps that could not be taken earlier in developed countries during its rapid technological growth. Thus genetically modified food, car and industrial emissions, smoking, and deforestation are some examples of the global issues that need careful investigation in search of the causes and remedies. High cancer mortality, increasingly more prevalent autoimmune disorder, and chronic respiratory ailments are now afflicting people of Morocco as much as the Republic of Italy.

Inflammatory responses are the first line of immune defences that involve body's innate immunity and prepare it for interaction with the acquired specific immunity. However, inflammatory responses can often become uncontrolled creating pathologic sequel depending on individual's genetic predisposition. Inflammation in brain could have severe consequences from mild oedema to serious afflictions such as Alzheimer's disease. Many studies showed that microglial inflammation may be linked to the onset or progression of Alzheimer's disease, meningioma and glioma-associated oedema [1].We are interested in determining the effects of air pollution on brain inflammation from two perspectives. The one involves study of how derangements due to inflammation affect nerve function, neurotransmitters release and ion channel function.
Indeed, increases the concentration of free calcium ions in the cytoplasm [Ca2 +] i, represent a major mechanism in cell signaling and are responsible for the regulation of a large number of diverse cellular responses [2, 3]. The influx of Ca2 + is involved in the transcription of some genes and as such plays an important role in growth and cell proliferation. In addition, it is also involved in apoptosis and cell death [4]. However, deregulation of calcium signaling is
also involved in numerous pathologies. There are two sources of calcium for an increase in [Ca2 +] i: the release of intracellular calcium reserves (mainly the endoplasmic reticulum or sarcoplasmic) and a calcium entry from the extracellular medium [5], [6].
The T-type calcium channels (CAV3) represent a route of entry of calcium into excitable cells. They are activated by small depolarization of the plasma membrane and produce calcium current that rapidly inactivates. These channels play an important role in cellular excitability, especially in neurons [4], and are involved in many diseases, such as epilepsy, neuropathic pain, but also cardiac hypertrophy and cancer. It is the increased activity of T-type channels, which is often found in these pathological situations and the identification of selective inhibitors of T-type channels is a current issue. Many natural lipids that inhibit very effectively channels have been identified [6].
Specifically, the aim of this project is to establish the relationship between some neurological pathology induced by air pollution exposure and the deregulation of calcium signaling. We are also interested to identify new active ligands on T-type channels, possibly selective inhibitors, which are then evaluated for their therapeutic value
The findings of the proposed investigation will certainly be of value to larger scientific community, but more importantly, this will help discover underlying pathologic mechanisms, the causes of long-term effects and adjutants or bio-products from endogenous Moroccan herbal treasure. Indeed the World Health Organisation estimated that 80 % of developing countries population relies on traditional medicines, mostly plant drugs for their primary health care needs. Also modern pharmacopoeia still contains at least 25 % drugs derived from plants and many others which are synthetic analogues built on prototype compound isolated from plants [7]. In the Mediterranean region, Morocco offers a great diversity of plant species and contains approximately 4500 vascular species and sub species, about 900 of which are endemic (25 %) [8]. A portion of these plants are used in the folk medicine by the rural people who are precluded from the luxury to access to modern therapy, mainly for economic reasons, there being inexistence excellent treatises which recount their principal forms of applications, their pharmacological activities and their chemical composition.
As a result of such lack of information, the real potential of these plants has not been exploited by the government or entrepreneurs of our country. On other hand, the threats posed by overexploitation caused by increasing human population and extensive destruction of the plant-rich habitats of the Moroccan ecosystems lead to decrease of biodiversity of these natural resources. Hence it is important that more action-oriented plans have to be initiated to exploit the full potential of these resources and their biodiversity, bearing in mind their valuation, conservation and sustainable development.

Obiettivi della ricerca

Many neurodegenerative disorders are accompanied by chronic glial activation, which is characterized by the abundant production of proinflammatory cytokines, disrupts Ca2+ homeostasis and stimulates astrocyte reactivity. The mechanisms by which the plausible NO product by air inhalation would induces Ca2+ dysregulation are not completely defined. Here, we examined how acute and chronic exposure to CO2 affect Ca2+ influx via TRPCs. homeostasis in freshly dissociated and primary cultured mouse cortical astrocytes, we envisage to evaluate the effect of herbal extracts purified in our laboratory on T-type channels, possibly selective inhibitors, which are then evaluated for their therapeutic value. We will build on these studies by moving into organ/tissue to determine the plausible mechanism of air pollution induced brain inflammation.

Ultimo aggiornamento: 23/11/2024