La relazione tra malattie neurodegenerative (NDD) e i disturbi neuropsichiatrici (NPD)

Abstract

Le malattie neurodegenerative (NDD) e i disturbi neuropsichiatrici (NPD) sono due cause comuni di morte negli anziani, inducendo morte progressiva delle cellule neuronali e i cambiamenti comportamentali. Le NDD comprendono il morbo di Alzheimer, il morbo di Parkinson, la malattia di Huntington, la sclerosi laterale amiotrofica, la sclerosi multipla e la malattia dei motoneuroni, caratterizzata da difetti cognitivi e disturbi della memoria, mentre i NPD comprendono depressione, convulsioni, emicrania, disturbi alimentari, dipendenze, paralisi, disturbi depressivi maggiori, disturbi d’ansia e schizofrenia, caratterizzati da cambiamenti comportamentali. Prove crescenti hanno dimostrato che le NDD e i NPD condividono meccanismi molecolari, che includono modifiche post-traduzionali, l’asse microbiota-intestino-cervello e meccanismi di segnalazione. È stato dimostrato che farmaci, vale a dire composti naturali, farmaci riproposti, ligandi diretti multi-bersaglio e a RNA, sono stati implementati come agenti terapeutici contro la NDD e i NPD. In questa tesi, mettiamo in evidenza i meccanismi molecolari condivisi, quali il ruolo dei fattori di rilascio caratteristici di ansia/stress, la segnalazione tra il citosol e il nucleo e l’asse microbiota-intestino-cervello nella fisiopatologia delle NDD e dei NPD.

Neurodegenerative diseases (NDDs) and neuropsychiatric disorders (NPDs) are two common causes of death in elderly people, which includes progressive neuronal cell death and behavioral changes. NDDs include Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, multiple sclerosis, and motor neuron disease, characterized by cognitive defects and memory impairment, whereas NPDs include depression, seizures, migraine headaches, eating disorders, addictions, palsies, major depressive disorders, anxiety, and schizophrenia, characterized by behavioral changes. Mounting evidence demonstrated that NDDs and NPDs share an overlapping mechanism, which includes post-translational modifications, the microbiota–gut–brain axis, and signaling events. Mounting evidence demonstrated that various drug molecules, namely, natural compounds, repurposed drugs, multitarget directed ligands, and RNAs, have been potentially implemented as therapeutic agents against NDDs and NPDs. Herein, we highlighted the overlapping mechanism, the role of anxiety/stress-releasing factors, cytosol-tonucleus signaling, and the microbiota–gut–brain axis in the pathophysiology of NDDs and NPDs. We summarize the therapeutic application of natural compounds, repurposed drugs, and multitarget-directed ligands as therapeutic agents. Lastly, we briefly described the application of RNA interferences as therapeutic agents in the pathogenesis of NDDs and NPDs.