Protein synthesis modulation as a therapeutic approach for amyotrophic lateral sclerosis and frontotemporal dementia

Protein synthesis is essential for cells to perform life metabolic processes.Pathological alterations of protein content can lead to particular diseases.Cells have an intrinsic array of mechanisms and pathways that are activated when protein misfolding,accumulation,aggregation or mislocalization occur.Some of them(like the unfolded protein response)represent complex interactions between endoplasmic reticulum sensors and elongation factors that tend to increase expression of chaperone proteins and/or repress translation in order to restore protein homeostasis(also known as proteostasis).This is even more important in neurons,as they are very susceptible to harmful effects associated with protein overload and proteostatic mechanisms are less effective with age.Several neurodegenerative pathologies such as Alzheimer’s,Parkinson’s,and Huntington’s diseases,amyotrophic lateral sclerosis and frontotemporal dementia exhibit a particular molecular signature of distinct,unbalanced protein overload.In amyotrophic lateral sclerosis and frontotemporal dementia,the majority of cases present intracellular inclusions of ubiquitinated transactive response DNA-binding protein of 43 kDa(TDP-43).TDP-43 is an RNA binding protein that participates in RNA metabolism,among other functions.Dysregulation of TDP-43(e.g.aggregation and mislocalization)can dramatically affect neurons,and this has been linked to disease development.Expression of amyotrophic lateral sclerosis/frontotemporal dementia TDP-43-related mutations in cellular and animal models has been shown to recapitulate key features of the amyotrophic lateral sclerosis/frontotemporal dementia disease spectrum.These variants can be causative of degeneration onset and progression.Most neurodegenerative diseases(including amyotrophic lateral sclerosis and frontotemporal dementia)have no cure at the moment;however,modulating translation has recently emerged as an attractive approach that can be performed at several steps(i.e.regulating activation of initiation and elongation factors,inhibiting unfolded protein response activation or inducing chaperone expression and activity).This review focuses on the features of protein imbalance in neurodegenerative disorders and the relevance of developing therapeutical compounds aiming at restoring proteostasis.We strive to highlight the importance of research on drugs that,not only restore protein imbalance without compromising translational activity of cells,but are also as safe as possible for the patients.

Synthesis Characterization and Biological Activities of an Enamine Derivative and Its Coordination Compounds

The medicinal uses and applications of metal complexes are of increasing clinical and commercial importance;this is as a result of some level of success achieved so far. In this regard, novel enamine free-base ligands were synthesized by the condensation of terephthalaldehyde and 2-(methylamino)ethanol. This afforded a dinegative ONNO donor enamine, free base, characterized using 1H and 13C NMR, Fourier-transformed infrared and UV-vis spectroscopy. Coordination compounds of the enamine were also synthesized using Cu(II), Ni(II), Co(II) and VO(IV) ions. These complexes were characterized by electronic, IR spectrophotometry, mass spectrometry, magnetic susceptibility and EDX. The compounds were thereafter evaluated for their antimicrobial and cytotoxic activities. The data obtained were supportive of an octahedral geometry for the Cu(II) complex, a square-pyramidal geometry for the vanadium complex and a 4-coordinate square-planar geometry for both the cobalt and nickel complexes. The magnetic susceptibility data revealed that the complexes are magnetically dilute and mononuclear with exception of the cobalt complex. The ligands and the complexes did not exhibit significant antimicrobial and cytotoxic assays, indicative of the nontoxicity of the ligand and complexes.

Pharmaceutical and nutraceutical potential of natural bioactive pigment:astaxanthin

Astaxanthin(3,3′-dihydroxy-β,β-carotene-4,4′-dione)is an orange-red,lipophilic keto-carotenoid pigment.It is majorly found in marine ecosystems particularly in aquatic animals such as salmon,shrimp,trout,krill,crayfish,and so on.It is also synthesized in microalgae Heamatococcus pluvialis,Chlorococcum,Chlorella zofingiensis,red yeast Phaffia rhodozyma and bacterium Paracoccus carotinifaciens.Some aquatic and terrestrial creatures regarded as a primary and secondary sources of the astaxanthin producing and accumulating it through their metabolic pathways.Astax-anthin is the powerful antioxidant,nutritional supplement as well as promising therapeutic compound,observed to have activities against different ravaging diseases and disorders.Researchers have reported remarkable bioactivities of astaxanthin against major non-communicable chronic diseases such as cardiovascular diseases,cancer,diabetes,neurodegenerative,and immune disorders.The current review discusses some structural aspects of astaxanthin.It fur-ther elaborates its multiple potencies such as antioxidant,anti-inflammatory,anti-proliferative,anti-cancer,anti-obese,anti-diabetic,anti-ageing,anti-TB,anti-viral,anti-COVID 19,neuro-protective,nephro-protective,and fertility-enhanc-ing properties.These potencies make it a more precious entity in the preventions as well as treatments of prevalent systematic diseases and/or disorders.Also,the review is acknowledging and documenting its powerful bioactivities in relation with the pharmaceutical as well as nutraceutical applicability.