Huperzine A and Its Neuroprotective Molecular Signaling in Alzheimer’s Disease

Abstract

Huperzine A (HupA), an alkaloid found in the club moss Huperzia serrata, has been used for centuries in Chinese folk medicine to treat dementia. The effects of this alkaloid have been attributed to its ability to inhibit the cholinergic enzyme acetylcholinesterase (AChE), acting as an acetylcholinesterase inhibitor (AChEI). The biological functions of HupA have been studied both in vitro and in vivo, and its role in neuroprotection appears to be a good therapeutic candidate for Alzheimer´s disease (AD). Here, we summarize the neuroprotective effects of HupA on AD, with an emphasis on its interactions with different molecular signaling avenues, such as the Wnt signaling, the pre- and post-synaptic region mechanisms (synaptotagmin, neuroligins), the amyloid precursor protein (APP) processing, the amyloid-β peptide (Aβ) accumulation, and mitochondrial protection. Our goal is to provide an integrated overview of the molecular mechanisms through which HupA affects AD.

Research progress in traditional Chinese medicine in the treatment of Alzheimer’s disease and related dementias

“…Moreover, HupA could restore Fe 2+ homeostasis in the brain. These findings further support that HupA may significantly slow the neuronal death process ( Friedli and Inestrosa, 2021 ).…”

Promising Molecular Targets in Pharmacological Therapy for Neuronal Damage in Brain Injury

“…Otherwise, this contribution stimulates the search in nature for new molecular drugs for neurodegenerative diseases possessing selective mechanisms of action and lacking undesired side effects, as shown in experiments with CGP37157. In the past, the discovery of huperazine A, a Chinese herbal medicine investigated for the treatment of Alzheimer's disease, entailed a breakthrough in the study of new highly selective inhibitors of acetylcholinesterase, as an example [102].…”

Micro- and Nanosized Carriers for Nose-to-Brain Drug Delivery in Neurodegenerative Disorders

“…Meng et al developed Huperzine A (HupA)-loaded mucoadhesive polylactide-co-glycoside (PLGA) nanoparticles with surface modification by lactoferrin (Lf)-conjugated N-trimethylated chitosan (TMC) (HupA Lf-TMC NPs) for efficient intranasal delivery to the brain for AD treatment. Huperzine A is a naturally occurring sesquiterpene alkaloid [ 80 ]. It is a reversible inhibitor of acetylcholinesterase and improves memory in behavioral animal models [ 81 ].…”