Single-neuron neurodegeneration as a degenerative model for Parkinson’s disease

The positive effect of levodopa in the treatment of Parkinson’s disease,although it is limited in time and has severe side effects,has encouraged the scientific community to look for new drugs that can stop the neurodegenerative process or even regenerate the neuromelanin-containing dopaminergic nigrostriatal neurons.Successful preclinical studies with coenzyme Q10,mitoquinone,isradipine,nilotinib,TCH346,neurturin,zonisamide,deferiprone,prasinezumab,and cinpanemab prompted clinical trials.However,these failed and after more than 50 years levodopa continues to be the key drug in the treatment of the disease,despite its severe side effects after 4–6 years of chronic treatment.The lack of translated successful results obtained in preclinical investigations based on the use of neurotoxins that do not exist in the human body as new drugs for Parkinson’s disease treatment is a big problem.In our opinion,the cause of these failures lies in the experimental animal models involving neurotoxins that do not exist in the human body,such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine,that induce a very fast,massive and expansive neurodegenerative process,which contrasts with the extremely slow one of neuromelanin-containing dopaminergic neurons.The exceedingly slow progress of the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s patients is due to(i)a degenerative model in which the neurotoxic effect of an endogenous neurotoxin affects a single neuron,(ii)a neurotoxic event that is not expansive and(iii)the fact that the neurotoxin that triggers the neurodegenerative process is produced inside the neuromelanin-containing dopaminergic neurons.The endogenous neurotoxin that fits this degenerative model involving one single neuron at a time is aminochrome,since it(i)is generated within neuromelanin-containing dopaminergic neurons,(ii)does not cause an expansive neurotoxic effect and(iii)triggers all the mechanisms involved in the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s disease.In conclusion,based on the hypothesis that the neurodegenerative process of idiopathic Parkinson’s disease corresponds to a single-neuron neurodegeneration model,we must search for molecules that increase the expression of the neuroprotective enzymes DT-diaphorase and glutathione transferase M2-2.It has been observed that the activation of the Kelch-like ECH-associated protein 1/nuclear factor(erythroid-derived 2)-like 2 pathway is associated with the transcriptional activation of the DT-diaphorase and glutathione transferase genes.

Subclinical hearing loss associated with aging

Objective:Contribute to clarifying the existence of subclinical hearing deficits associated with aging.Design:In this work,we study and compare the auditory perceptual and electrophysiological performance of normal-hearing young and adult subjects(tonal audiometry,high-frequency tone threshold,a triplet of digits in noise,and click-evoked auditory brainstem response).Study sample:45 normal hearing volunteers were evaluated and divided into two groups according to age.27 subjects were included in the“young group”(mean 22.1 years),and 18 subjects(mean 42.22 years)were included in the“adult group.”Results:In the perceptual tests,the adult group presented significantly worse tonal thresholds in the high frequencies(12 and 16 kHz)and worse performance in the digit triplet tests in noise.In the electrophysiological test using the auditory brainstem response technique,the adult group presented significantly lower I and V wave amplitudes and higher V wave latencies at the supra-threshold level.At the threshold level,we observed a significantly higher latency in wave V in the adult group.In addition,in the partial correlation analysis,controlling for the hearing level,we observed a relationship(negative)between age and speech in noise performance and high-frequency thresholds.No significant association was observed between age and the auditory brainstem response.Conclusion:The results are compatible with subclinical hearing loss associated with aging.

Role of copper nanoparticles in wound healing for chronic wounds:literature review

Chronic wounds are defined as wounds that fail to proceed through the normal phases of wound healing in an orderly and timely manner.The most common and inevitable impairment to wound healing is the installation of an infection,usually in the case of chronic wounds.Therefore,the objective of the present review was to identify the importance of copper nanoparticles in dressings for wound healing.Nanoparticles such as silver,gold and copper combat infectious processes through the inhibition of protein synthesis,peroxidation of the cell membrane and destroying the nucleic acids of bacteria and viruses.Among bioactive nanoparticles,copper plays a complex role in various cells,it modulates several cytokines and growth factor mechanisms of action and is essentially involved in all stages of the wound healing process.More importantly,copper plays a key role in skin regeneration and angiogenesis and accelerates the healing process through induction of vascular endothelial growth factor(VEGF)and angiogenesis by hypoxia-induced factor-1-alpha(HIF-1α)action where copper enhances HIF-1αexpression and HIF-1αbinding to the critical motifs in the promoter and putative enhancer regions of HIF-1-regulated genes.