Anti-Alzheimer's Molecules Derived from Marine Life: Understanding Molecular Mechanisms and Therapeutic Potential.

Md Tanvir Kabir,Jesus Simal-Gandara,Md Sahab Uddin,Philippe Jeandet,Saikat Mitra,Talha Bin Emran,Mohamed M Abdel-Daim,Amany A Sayed,Ghadeer M Albadrani

doi:10.3390/md19050251

Abstract

Alzheimer’s disease (AD) is a devastating neurodegenerative disease and the most common cause of dementia. It has been confirmed that the pathological processes that intervene in AD development are linked with oxidative damage to neurons, neuroinflammation, tau phosphorylation, amyloid beta (Aβ) aggregation, glutamate excitotoxicity, and cholinergic deficit. Still, there is no available therapy that can cure AD. Available therapies only manage some of the AD symptoms at the early stages of AD. Various studies have revealed that bioactive compounds derived from marine organisms and plants can exert neuroprotective activities with fewer adverse events, as compared with synthetic drugs. Furthermore, marine organisms have been identified as a source of novel compounds with therapeutic potential. Thus, there is a growing interest regarding bioactive compounds derived from marine sources that have anti-AD potentials. Various marine drugs including bryostatin-1, homotaurine, anabaseine and its derivative, rifampicins, anhydroexfoliamycin, undecylprodigioisin, gracilins, 13-desmethyl spirolide-C, and dictyostatin displayed excellent bioavailability and efficacy against AD. Most of these marine drugs were found to be well-tolerated in AD patients, along with no significant drug-associated adverse events. In this review, we focus on the drugs derived from marine life that can be useful in AD treatment and also summarize the therapeutic agents that are currently used to treat AD.

Highlights

Alzheimer’s disease (AD) is widely known as the most common cause of dementia, and AD is most frequently observed in older individuals [1,2]
We focus on the drugs derived from marine organisms that can be useful in AD treatment
1 (LRP1) and P-glycoprotein (P-gp) at the blood–brain barrier (BBB) [93]. These findings suggest the existence of a probable receptor/transporter that has a significant contribution in the clearance of Aβ, which was found to be elevated by rifampicin [94]

Summary

Introduction

Alzheimer’s disease (AD) is widely known as the most common cause of dementia, and AD is most frequently observed in older individuals [1,2]. It has been reported that early-onset AD development is linked with various genetic mutations, in amyloid precursor protein (APP), PSEN1, and preselinin 2 (PSEN2) genes [6]. Dysregulated expression of these genes might be present in around 5–10% of diagnosed cases of early-onset AD [4,6]. The ocean serves as a source of numerous bioactive substances; the ocean is still largely unexploited [24,25,26,27] It was revealed through the isolation of soft corals that marine organisms can be an important source for novel drugs containing novel chemical structures and an increased level of therapeutic value. We summarize the therapeutic agents that are currently used to treat AD

Current Alzheimer’s Drug Therapy

Preclinical Evidence

Clinical Evidence

Anhydroexfoliamycin and Undecylprodigioisin

Gracilins

Conclusions