Low‐molecular mimetics of nerve growth factor and brain‐derived neurotrophic factor: Design and pharmacological properties

Abstract

To overcome the limitations of the clinical use of neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), scientists have been trying to create their low-molecular-weight mimetics having improved pharmacokinetic properties and lacking side effects of full-sized proteins since the 90s of the last century. The efforts of various research groups have led

Peptides Derived from Growth Factors to Treat Alzheimer’s Disease

“…They also associate noncovalently into homodimers, with each monomer presenting a cysteine “knot” with the characteristic loop formation and a tertiary fold. These monomers (118 or 119 amino acids) are characterized by seven β-strands connected by three exposed β-turn loops (L1, L2, L4) and an additional loop L3 ( Figure 1 ) [ 58 , 59 ]. All of these exposed sites may be accessible for interaction with neurotrophin receptors.…”

“…To overcome the limitations encountered using native growth factors, alternative strategies involving biologically active small peptides have been developed ( Table 2 ), in order to improve pharmacokinetic properties and BBB permeability, selectively activate targeted signaling pathways (biased signaling), and decrease the side effects compared to full-sized proteins [ 59 , 185 ]. Figure 4 summarizes the signaling pathways induced by the peptides and their subsequent effect on neuronal differentiation, cholinergic phenotype, and cell survival in vitro and/or in vivo.…”

“…The dimeric peptide GK-2 (described in the subsection “Peptides derived from mNGF L1-L4 loops”) had neuroprotective activities in several experimental models. It stimulated neuroprotective and neurogenesis activities in vivo in a rat model of ischemic stroke ( Table 2 ) [ 235 ] and in several other experimental models of traumatic brain injury or degenerative diseases [ 59 , 260 , 261 ]. GK-2 counteracts the impaired cognitive functions in two AD rat models: (1) a surgical one (transection of the septo-hippocampal pathway), resulting in the development of cholinergic deficiency; and (2) a neurotoxic one (streptozotocin), reproducing the main pathological hallmarks (Aβ accumulation and tau phosphorylation) ( Table 2 ) [ 234 ].…”

Neurodegenerative disorders—Searching for targets and new ways of diseases treatment

“…Gudasheva et al reviews the relationship between the structure of the mimetics, mechanism of action and pharmacological properties. 14 Another group of short peptides, in particular, glyproline peptides, their effect on fat and carbohydrate metabolism and perspectives for their use as protective therapeutic agents critically analysed by N. Mysoedov et. al.…”

“…Low molecular weight of mimetics of neurotrophins nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF) were developed for therapy of various diseases including neurological disorders. Gudasheva et al reviews the relationship between the structure of the mimetics, mechanism of action and pharmacological properties 14 …”