Multi-target Natural and Nature-Inspired Compounds against Neurodegeneration: A Focus on Dual Cholinesterase and Phosphodiesterase Inhibitors

Alzheimer’s disease is a memory-related neurodegenerative condition leading to cognitive impairment. Cholinergic deficit, together with other underlying mechanisms, leads the onset and progression of disease. Consequently, acetylcholinesterase inhibitors are used for symptomatic treatment dementia, even if limited efficacy observed. More recently, some specific phosphodiesterase isoforms emerged as promising, alternative targets developing contrast neurodegeneration. Phosphodiesterase 4, 5 9 were found be expressed in brain regions that relevant cognition. Given complex nature combination involved biochemical development polypharmacological agents acting on more than one pathway desirable. This review provides an overview recent reports focused natural Nature-inspired small molecules, or plant extracts, dual cholinesterase inhibitors. In context multi-target directed ligand approach, such molecules would pave way novel against precisely, according literature data, xanthines, alkaloids, flavonoids, coumarins polyphenolic acids represent promising scaffolds future optimization.