diseases

摘要： Vision is one of our most precious senses,and its impairment has a high socio-economic impact.In the industrialized world,degenerative diseases of the retina lead to vision loss,particularly among the elderly.These degenerations include,for instance,retinitis pigmentosa,age-related macular degeneration,and diabetic retinopathy.Although treatments are evolving to manage late-stage symptoms of retinal degenerations,no effective therapies to recover vision loss exist.Retinal degeneration often involves loss or damage to specialized neural cells,such as photoreceptors,and their death stimulates the activation and proliferation of Müller cells(Salman et al.,2021).

摘要： Importance of TAU protein for dementia syndromes:Dementia currently affects about 55 million people worldwide,with Alzheimer's disease(AD)being the most prevalent form.The one crucial pathological hallmark of AD that correlates best with loss of synapses and cognitive decline are the so-called intracellular neurofibrillary tangles composed of mislocalized/missorted and hyperphosphorylated TAU protein(Naseri et al.,2019).Many other neurodegenerative diseases,both genetic and nongenetic,are characterized by neurofibrillary ta ngles or pathological accumulation of the protein TAU and are thus termed"tauopathies".

摘要： Brain synapses play a key role in neuronal communication:this“conversation”is at the basis of all brain activities and synaptic dysfunction leads to brain disorders.We study the modulators of this crucial synaptic function and we here present the evidence supporting the c-Jun N-terminal kinase(JNK)pathway as a pivotal actor in this scenario.

摘要： Discovered in pig brains in 1982,the brain-derived neurotrophic factor(BDNF)is one of the most studied and characterized neurotrophins in the central nervous system.In recent years,BDNF has received considerable attention for its importance in the development and maintenance of normal brain function.This is because BDNF plays an important role in crucial functions of the nervous system,such as the survival,differentiation,and maturation of neurons and glial cells as well as the actions of neuroprotection in adverse conditions,such as glutamatergic overstimulation,cerebral ischemia,hypoglycemia,and neurotoxicity(Kowiański et al.,2018).

摘要： Background:Nanotechnologies promise to improve disease diagnosis and treatment,overcoming the limitations of conventional administrations.In particular,extracellular vesicles(EVs)and artificial vesicles(AVs)are strongly emerging tools in nanomedicine(Leggio et al.,2020).EVs are cell-derived membrane structures secreted after the fusion of endosomes with the plasma membrane(exosomes)or shed from the plasma membrane(microvesicles).EVs are released by different brain cells(neurons,oligodendrocytes,astrocytes,and microglia)and constitute a physiological intercellular communication system.Indeed,EVs can deliver different types of molecules(nucleic acids and proteins),which often influence the phenotype of the recipient cells.They play a physiological role in the central nervous system(CNS),such as development,myelination,regeneration,and synaptic activity(Lai et al.,2012).Due to their content,EVs could therefore constitute an important biomarker for neurodegenerative diseases,represent candidates for therapeutic use,enclosing regulatory molecules,or be considered as vectors for brain drug delivery(Croese et al.,2018).

摘要： In recent years,large animal models of naturally occurring diseases have become increasingly studied,with the rationale that their disease attributes may better recapitulate the pathological features of corresponding human diseases as compared to induced disease models(Hoffman and Dow,2016).Of the available naturally occurring disease models,the canine is increasingly recognized as a valuable pre-clinical animal model in translational medicine for numerous human diseases,including cancer.

摘要： Alzheimer's disease is the most prevalent type of dementia today,discovered and described by Alois Alzheimer in 1907.According to the World Alzheimer Report 2021,75%of people with dementia worldwide are undiagnosed,equivalent to 41 million people(Gauthier et al.,2021).With each passing year,the number of people affected by these diseases is increasing,and the estimates of suffering from them in the future are growing.

摘要： Protein misfolding and aggregation into amyloid fibrils is the main pathological hallmark of neurodegenerative diseases,including Alzheimer’s,Parkinson’s,Huntington’s,and prion diseases(Chiti and Dobson,2017).These insoluble fibrillar deposits possess a common structure characterized by a cross-β-sheet conformation in which β-strands run transversely to the fiber axis and form an intermolecular network of hydrogen bonds.

摘要： Unfortunately,ag ing is not a reversible phenomenon and the processes of senescence are unavoidable.However,the biological effects of aging may be turned back,and with those,it can be reduced risk of all age-related illnesses,such as cardiovascular diseases,cancer,diabetes,and neurodegenerative diseases,including Alzheimer’s disease(AD),and Parkinson’s diseases(PD).In the latest decades,scientists worldwide therefore have developed several strategies,either natural or pharmacological,to counteract aging phenomena,with the final goal to improve human life expectancy.The main scientific rationale beyond these strategies focuses on the opportunity to reduce chronic low-grade inflammation(inflammaging),the increase in oxidative stress damage,and the impairment in the immune system,all typical mechanisms of senescence(Verdaguer et al.,2012).

摘要： Synaptosome:Synapses are the most critical portion of neuron connections,necessary for cellular organization of the brain.Synapse integrity is uttermost important for healthy brain functioning.Any perturbation in the synapse structure and/or function initiates neurological disorders.Synapses are the prime targets that are smashed in almost all neurodegenerative diseases.The vital components of synapse are essential for neurotransmission,synaptic plasticity and overall synapse function.Synapse dysfunctions are well studied in Alzheimer’s disease(AD)and other neurodegenerative diseases(Gowda et al.,2021).The best way to study the synapse dysfunctions in neurological diseases is the biochemical analysis of“synaptosome”.

摘要： 本发明公开了一种利用连锁不平衡在家系中筛查Wilson disease基因突变的方法，它基于连锁不平衡原理，以单核苷酸多态性基因分型的方法，依靠6个单核苷酸多态性位点确定肝豆状核变性患者以及其兄弟姐妹(或者三级以内亲属)的基因型状态，将家系其他成员的单倍型与先证者的单倍型相比较判断是否为患病或杂合携带者。

摘要： 本发明公开了一种利用连锁不平衡在家系中筛查Wilson disease基因突变的方法，它基于连锁不平衡原理，以单核苷酸多态性基因分型的方法，依靠6个单核苷酸多态性位点确定肝豆状核变性患者以及其兄弟姐妹(或者三级以内亲属)的基因型状态，将家系其他成员的单倍型与先证者的单倍型相比较判断是否为患病或杂合携带者。