Chondroitin sulfate proteoglycans (CSPGs) are the most abundant components of glial scar formed after severe traumatic brain injury as well as spinal cord injury and play a crucial inhibitory role in axonal regeneration by selective contraction of filopodia of the growth cone of sprouting neurites. Healing of central nervous system (CNS) injury requires degradation of the glycosamine glycan backbone of CSPGs in order to reduce the inhibitory effect of the CSPG layer. The key focus of this Viewpoint is to address a few important regenerative approaches useful for overcoming the inhibitory barrier caused by chondroitin sulfate proteoglycans.
Amyloid-β
42(Aβ42), an enzymatically cleaved (1–42 amino acid long) toxic peptide remnant, has
long been reported to play the key role in Alzheimer’s disease
(AD). Aβ42 also plays the key role in the onset of other AD-related
factors including hyperphosphorylation of tau protein that forms intracellular
neurofibrillary tangles, imbalances in the function of the neurotransmitter
acetylcholine, and even generation of reactive oxygen species (ROS),
disrupting the cytoskeleton and homeostasis of the cell. To address
these issues, researchers have tried to construct several strategies
to target multiple aspects of the disease but failed to produce any
clinically successful therapeutic molecules. In this article, we report
a new peptoid called RA-1 that was designed and constructed from the
hydrophobic stretch of the Aβ42 peptide, 16KLVFFA21. This hydrophobic stretch is primarily responsible for the
Aβ42 peptide aggregation. Experimental study showed that the
RA-1 peptoid is stable under proteolytic conditions, can stabilize
the microtubule, and can inhibit the formation of toxic Aβ42
aggregates by attenuating hydrophobic interactions between Aβ42
monomers. Furthermore, results from various intracellular assays showed
that RA-1 inhibits Aβ42 fibril formation caused by the imbalance
in AchE activity, reduces the production of cytotoxic reactive oxygen
species (ROS), and promotes neurite outgrowth even in the toxic environment.
Remarkably, we have also demonstrated that our peptoid has significant
ability to improve the cognitive ability and memory impairment in in vivo rats exposed to AlCl3 and d-galactose
(d-gal) dementia model. These findings are also validated
with histological studies. Overall, our newly developed peptoid emerges
as a multimodal potent therapeutic lead molecule against AD.
Green synthesis of AuNPs that have potential anticancer properties is relatively simple, cheap and eco-friendly compared to the conventional chemical/physical approaches. Quercetin is known for its antioxidant and anticancer properties, i.e., induction of apoptosis, tumour suppression, etc. This study aims to characterize and compare between two differentially synthesized Quercetin-Au-Nanoconjugates, Q-Au-NCTSC and Q-AU-NCLE using a pure biochemical reductant, trisodium citrate and its natural alternative, citrus lemon extract respectively. Antibacterial and anticancer effects of both the nanoconjugates would also be checked and compared to analyze whether the use of a lemon extract has any impact on its structure and functional properties. A series of physicochemical characterizations viz. UV-Vis spectrophotometry, DLS, Zeta Potential, FT-IR, and SEM of the nanoconjugates were done. Further, evaluation of in vitro antibacterial activity was done against two Gram-positive bacteria: Staphylococcus aureus; Bacillus Subtilis; and two Gram-negative bacteria: Pseudomonas aeruginosa; Klebsiella pneumonia and cytotoxicity efficacy were checked on breast cancer (MCF7) cell line. Effective reduction of Au+3 to Au0 with quantum confinement in nano-regime was confirmed by a change of bulk colour of the HAu+3Cl4 solution, whereas conjugation of Quercetin to AuNPs was confirmed by FTIR. DLS showed the average size of the Q-Au-NCTSC and Q-Au-NCLE are 30 nm and 35.6 nm, respectively. The Q-Au-NCLE has shown comparatively better stability and antibacterial activity. In the case of cytotoxicity study on MCF7 cell line, the Q-Au-NCLE showed better efficacy (cell death ~ 75%) with respect to Q-Au-NCTSC (cell death ~66%). Natural sources rich in citric acid would serve as the best alternative to tri-sodium citrate in the synthesis of Au-NPs and different nanoconjugates for biomedical applications.
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