Relationship between lysophospholipids and Alzheimer's disease: in search of the pharmacological target of the future
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Marta Moreno-Rodríguez Jonatan Martínez-Gardeazabal Iker Bengoetxea de Tena Estíbaliz González de San Román Laura Lombardero Alberto Llorente-Ovejero
Rafael Rodríguez-Puertas
Abstract
In addition to energy and structural functions, lipids are becoming important thanks to the other functions described. Some lipids have been shown to exhibit neurotransmitter or neuromodulatory function, including lysophospholipids. Lysophospholipids are small bioactive lipid molecules that are distinguished only by having a single carbon chain and a single polar head. The lysophosphatidic acid and sphingosine 1-phosphate structure and system functions are best described among those with neurotransmitter function. Lysophospholipids act as extracellular mediators that activate receptor-specific G proteins that are specific to them. The signaling of these molecules modulate certain neurochemical processes, including neuromodulation and neuroinflammation. They have also presented the relationship with learning and memory. In this respect, the best described lysophospholipid systems, lysophosphatidic acid and sphingosine 1-phosphate, are indeed disturbed in Alzheimer's disease and in some animal models of this disease. The meaning of these changes is not yet established, but their effect may be related to the modulation of other neurotransmission systems or other biological functions. These lipids are therefore supposed to be the promising pharmacological targets to alleviate the neuropathological and neuropsychiatric symptoms that appear in Alzheimer's disease. Therefore, marketed drugs that have lipid signaling as a pharmacological target and that are useful to treat other neurodegenerative diseases could be also helpful to treat the Alzheimer’s disease, and with this it might be possible to fill the pharmacological gap in the treatment of Alzheimer's disease so far.
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lysophospholipids, sphingosine 1-phosphate, lysophosphatidic acid, Alzheimer’s disease, neurolipids, neuromodulation