Current and Prospective Treatments for Alzheimer's Disease (and Other Neurodegenerative Diseases)

Pedrini, Steve; Morici, Mike; Martins, Ralph N.

doi:10.1002/9781119356752.ch14

Cited by 1 publication

(1 citation statement)

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“…A range of therapeutic approaches for AD-associated proteopathies are therefore in various stages of development, including enzyme inhibitors targeting the production pathway of amyloid-beta (Kumar et al, 2018), gene silencing technologies to limit the expression of pro-aggregatory mutant tau proteins (Miller et al, 2004), kinase inhibitors aimed at preventing the pro-aggregatory hyperphosphorylation of tau, passive and active immunotherapies developed to drive protein clearance, and small molecule inhibitors of protein aggregation. These strategies are comprehensively reviewed in the literature (Hardy and De Strooper, 2017;Congdon and Sigurdsson, 2018;Pedrini et al, 2019). It remains unclear whether the proteopathies observed in AD are causative or consequential with regards to other aspects of AD pathogenesis, such as inflammation, neurovascular dysfunction, and metabolic disorders.…”

Section: Introductionmentioning

confidence: 99%

Arginine and Arginine-Rich Peptides as Modulators of Protein Aggregation and Cytotoxicity Associated With Alzheimer’s Disease

Mamsa

Meloni

2021

Front. Mol. Neurosci.

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A substantial body of evidence indicates cationic, arginine-rich peptides (CARPs) are effective therapeutic compounds for a range of neurodegenerative pathologies, with beneficial effects including the reduction of excitotoxic cell death and mitochondrial dysfunction. CARPs, therefore, represent an emergent class of promising neurotherapeutics with multimodal mechanisms of action. Arginine itself is a known chaotrope, able to prevent misfolding and aggregation of proteins. The putative role of proteopathies in chronic neurodegenerative diseases such as Alzheimer’s disease (AD) warrants investigation into whether CARPs could also prevent the aggregation and cytotoxicity of amyloidogenic proteins, particularly amyloid-beta and tau. While monomeric arginine is well-established as an inhibitor of protein aggregation in solution, no studies have comprehensively discussed the anti-aggregatory properties of arginine and CARPs on proteins associated with neurodegenerative disease. Here, we review the structural, physicochemical, and self-associative properties of arginine and the guanidinium moiety, to explore the mechanisms underlying the modulation of protein aggregation by monomeric and multimeric arginine molecules. Arginine-rich peptide-based inhibitors of amyloid-beta and tau aggregation are discussed, as well as further modulatory roles which could reduce proteopathic cytotoxicity, in the context of therapeutic development for AD.

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