Pharmacotherapeutic targets in Alzheimer's disease

Abstract

• Current pharmacotherapies for the treatment of AD • AD pharmacotherapies targeting τ ‐ Modulators of – kinases or phosphatases ‐ τ aggregation inhibitors (TAIs) • AD pharmacotherapies targeting Aβ ‐ Inhibitors and/or modulators of the secretases ‐ Aβ aggregation inhibitors ‐ Passive or active immunization • The metal hypothesis of AD • AD pharmacotherapies targeting metal ions ‐ Antioxidants ‐ Metal chelators ‐ Metal complexes ‐ Metal‐protein attenuating compounds Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder which is characterized by an increasing impairment in normal memory and cognitive processes that significantly diminishes a person's daily functioning. Despite decades of research and advances in our understanding of disease aetiology and pathogenesis, there are still no effective disease‐modifying drugs available for the treatment of AD. However, numerous compounds are currently undergoing pre‐clinical and clinical evaluations. These candidate pharma‐cotherapeutics are aimed at various aspects of the disease, such as the microtubule‐associated τ‐protein, the amyloid‐β (Aβ) peptide and metal ion dyshomeostasis – all of which are involved in the development and progression of AD. We will review the way these pharmacological strategies target the biochemical and clinical features of the disease and the investigational drugs for each category.