Therapeutic potential of ApoE-mimetic peptides in CNS disorders: Current perspective

Abstract

The prevalence and burden of CNS disorders are increasing significantly due to the increase in life span and population. The contemporary need in CNS drug discovery is to develop the therapy that can halt the disease progression (disease-modifying therapy). While developing such CNS therapies, the major bottleneck is the blood-brain barrier (BBB) impermeability of drugs that influences the development of effective therapies to treat various CNS disorders. Since the influential innovation of insulin to treat diabetic patients in the 1920s, a lot of attention has been given for producing therapeutic proteins and peptides as remedies for several diseases, including neurological disorders. Recently, researchers have explored therapeutic potential of apolipoprotein E (ApoE)-mimetic peptides in the same context. ApoE is the major apolipoprotein produced in the brain by the astrocytes and plays a significant role in the formation of synapses, myelination, and neuronal proliferation. ApoE can be a potential candidate for treating CNS disorders. However, the large size of the ApoE leads to the BBB impermeability that restricts its use in native form. This problem can be overcome by developing small ApoE-mimetic peptides with good BBB permeability and similar biological function as native ApoE. Various ApoE-mimetic peptides have been developed and investigated in different CNS disorders. This review provide insights into the latest development of ApoE and its mimetic peptides in CNS disorders, along with their beneficial outcomes.