An Alternate View of Neuroprotection with Peptides in Alzheimer’s Disease

Abstract

Neuroprotection plays a crucial role in everyday life, maintaining a clean environment in the central nervous system to allow for normal functioning. In Alzheimer's disease and other neurodegenerative disorders, neuroprotection may have two roles. Under standard circumstances, the immune system protects the CNS, but sometimes it can exacerbate the pathophysiology of some diseases through neuroinflammation leading to further degeneration. Alzheimer's disease is fast getting out of control, with no new approvals in therapeutics since 2003, and of those approved, all target symptomatic treatment. Initiated by a microglial response to Aβ plaques, therapeutic development should focus on the amyloid cascade as a neuroprotective measure for Alzheimer's disease. This chapter will examine the status of the types of therapeutics in clinical trials for Alzheimer's disease, offering insights into peptides as an area of opportunity for neuroprotection and detailing considerations for the use of peptides in Alzheimer's disease.

Subcommissural Organ-Spondin-Derived Peptide Restores Memory in a Mouse Model of Alzheimer’s Disease

“…Peptides are highly selective, efficient, and well-tolerated drugs, with better safety profiles compared to those of small molecules, antibodies and biologics ( Fosgerau and Hoffmann, 2015 ). Over 70 peptide drugs are marketed worldwide and more than 150 are in different phases of clinical trials ( Lau and Dunn, 2018 ; Lee and Hur, 2019 ; King and Suphioglu, 2020 ). Indeed, the development of peptide therapeutics includes peptide inhibitors of Aβ and β-site amyloid precursor protein (APP) cleaving enzyme 1 for the treatment of AD ( Baig et al, 2018 ; King and Suphioglu, 2020 ).…”

“…Over 70 peptide drugs are marketed worldwide and more than 150 are in different phases of clinical trials ( Lau and Dunn, 2018 ; Lee and Hur, 2019 ; King and Suphioglu, 2020 ). Indeed, the development of peptide therapeutics includes peptide inhibitors of Aβ and β-site amyloid precursor protein (APP) cleaving enzyme 1 for the treatment of AD ( Baig et al, 2018 ; King and Suphioglu, 2020 ). NX210 is a small peptide designed from the most conserved sequence of the TSR1 motif of SCO-spondin and has two cysteines that create a disulfide bond under oxidative conditions, resulting in an alternative cyclic form of NX210, designated NX210c.…”