Target-Based Drug Delivery Approaches against Alzheimer’s Disease – Recent Updates

Millions of people worldwide suffer from Alzheimer's disease (AD), a crippling neurological illness. The ongoing rise of AD necessitates the rapid development of effective preventive and therapeutic approaches. Existing pharmacologic treatments for AD are divided into two categories: acetylcholinesterase (AChE) inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists, both of which have numerous adverse effects and are largely ineffective in slowing disease progression. Current treatments for AD face challenges such as limited bioavailability and the difficulty of crossing the brain's protective barriers, known as the Blood-Brain Barrier (BBB). The side effects of these drugs include dizziness, elevated blood pressure, constipation, vomiting, and cramping of abdominal muscles. In this review, we focus on novel targets, including the Tau protein, M1 mAChR, and PDE4s, along with their intricate mechanisms of action in AD, which have shown promising outcomes in numerous studies for successful treatment. Additionally, we discuss synthetic and herbal medications that act on these novel targets, including orthosteric agonists, allosteric compounds, and positive allosteric modulators (PAMs) of M1 mAChR, as well as taubased natural products as AD therapeutics. Examples include the microtubule stabilizer paclitaxel from the Pacific Yew Taxus brevifolia and the anti-amyloid agent curcumin, isolated from turmeric. The role of PDE4 in the coordination of cAMP response element-binding signaling in AD is also covered in this review. We highlight the advantages of specifically targeting PDE4D and discuss the use of herbal medications such as resveratrol, curcumin, 6-gingerol, and capsaicin, which are effective AD therapeutics and potential PDE4D inhibitors.