Current progress, challenges and future prospects of diagnostic and therapeutic interventions in Alzheimer's disease

Abstract

The diverse pathological mechanisms and their implications for the development of effective diagnostic and therapeutic interventions in Alzheimer's disease are presented with current progress, challenges and future prospects.

Role of Post‐translational Modifications in Alzheimer's Disease

“…In pathological conditions, APP is cleaved by β‐ and γ‐secretases to generate perilous peptides Aβ1 to 37/43. Aβ42 is highly hydrophobic and undergoes aggregation to form polymorphic species, such as oligomers, protofibrils, fibrillar aggregates and senile plaques, that cause neurodegeneration and memory deficiencies (Figure ) …”

“…A recent report revealed that 47 million people were affected by AD worldwide in 2015; this is expected to reach more than 135 million by 2050 . The number of deaths caused by major diseases, such as cancer, cardiovascular, and AIDS, are declining due to the availability of effective medication, whereas those as a result of AD have risen by more than 71 % . Thus, AD is a devastating disease that causes distress in patients and is a major health‐related economic burden to society .…”

“…Currently practised diagnostic methods are mostly based on visual symptoms, such as behavioural changes and cognitive decline, which are noticeable only in the advanced stage of the disease, in which significant irreversible damage has already occurred to the brain . With considerable advances in understanding of the disease pathology, diverse therapeutic strategies have been developed in recent decades to target cholinergic receptors, secretases, kinases, apolipoprotein E4 (ApoE4), Aβ and tau aggregation, Aβ clearance, oxidative stress, neuroinflammation and metabolic pathways . In recent years, a wide range of lead molecules, ranging from natural products to synthetic small molecules, peptides and peptidomimetics to antibodies with multifunctional activity to inhibit multifaceted toxicity of AD, have been developed .…”

“…With considerable advances in understanding of the disease pathology, diverse therapeutic strategies have been developed in recent decades to target cholinergic receptors, secretases, kinases, apolipoprotein E4 (ApoE4), Aβ and tau aggregation, Aβ clearance, oxidative stress, neuroinflammation and metabolic pathways . In recent years, a wide range of lead molecules, ranging from natural products to synthetic small molecules, peptides and peptidomimetics to antibodies with multifunctional activity to inhibit multifaceted toxicity of AD, have been developed . Some drug candidates fail at different stages of clinical trials, possibly due to the unreliability of the drug targets, inadequate design or side effects, while the in vivo efficacy of other drug candidates has yet to be evaluated.…”

Engineering Versatile Nanoparticles for Near‐Infrared Light‐Tunable Drug Release and Photothermal Degradation of Amyloid β

“…Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disease in which the deposition of extracellular senile plaques and the intracellular neurofibrillary tangles are the main hallmarks. [1][2][3] The deposition or misfolding of amyloid-β peptide (Aβ) is associated with the formation of senile plaques and therefore considered to be a key diagnostic target. [4,5] Aβ is derived from the amyloid precursor protein by sequential cleavage, via βand γ-secretases.…”