This Project aims at synthesising powerful chemical tools that make the neurotransmitter L-glutamate (L-Glu) detectable by fluorescence spectroscopy and permit to study its mobility, distribution and concentration in living cells with fluorescent microscopy, thus strongly contributing to the study of biologists and physiopathologists on neurological diseases in which this neurotransmitter seems to play an important role. L-Glu is the most abundant neurotransmitter of the excitatory synapses in the Central Nervous System (CNS). It is fundamental in the regulation and modulation of the CNS, in the regulation of the locomotive and physiological activity, in superior intellectual activity, and in affectivity and moods. Clinical studies have evidenced that metabolic damages of L-Glu are responsible of neurological and degenerative illnesses such as Parkinson, Alzheimer, Huntington, dementia, amyotrophic lateral sclerosis (ASL): in these pathologies L-Glu accumulates in extra-cellular space and becomes toxic for neurons. It is needed to investigate distribution and concentration of L-Glu directly in living cells but, the techniques available today, microdialyse and capillary electrophores, damage the living tissue. Fluorescence microscopy does not cause damages and provides sensitivity, selectivity and versatility but, L-Glu is not fluorescent by itself. In order to study it with fluorescent imaging techniques, we will synthesise chemical tools as: -a fluorescent L-Glu derivative: a synthetic molecule that can be inserted inside the cells and whose diffusion and distribution can be followed by imaging technique;-a fluorescent probe for L-Glu: selective receptors of L-Glu for determining distribution and concentration of L-Glu in extracellular space.The applicant, dr. Berni, and the Lacrem laboratory together can provide the multidisciplinary knowledge necessary to realise the Project: coordination chemistry, photo-physics, organic synthesis, analytical techniques.
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