Synthetic and Natural Bioactive Molecules in Balancing the Crosstalk among Common Signaling Pathways in Alzheimer’s Disease: Understanding the Neurotoxic Mechanisms for Therapeutic Intervention

Abstract

The structure and function of the brain greatly rely on different signaling pathways. The wide variety of biological processes, including neurogenesis, axonal remodeling, the development and maintenance of pre- and postsynaptic terminals, and excitatory synaptic transmission, depends on combined actions of these molecular pathways. From that point of view, it is important to investigate signaling pathways and their crosstalk in order to better understand the formation of toxic proteins during neurodegeneration. With recent discoveries, it is established that the modulation of several pathological events in Alzheimer’s disease (AD) due to the mammalian target of rapamycin (mTOR), Wnt signaling, 5′-adenosine monophosphate activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), and sirtuin 1 (Sirt1, silent mating-type information regulator 2 homologue 1) are central to the key findings. These include decreased amyloid formation and inflammation, mitochondrial dynamics control, and enhanced neural stability. This review intends to emphasize the importance of these signaling pathways, which collectively determine the fate of neurons in AD in several ways. This review will also focus on the role of novel synthetic and natural bioactive molecules in balancing the intricate crosstalk among different pathways in order to prolong the longevity of AD patients.