Search

• Multimodal strategies and interventions, e.g. healthy lifestyle (dietary and physical activity), can be recommended for treatment of Alzheimer's disease (AD). • Gene study and gene-based therapy with a critical role in the detection and cure of AD will have a fundamental role. • Attempts to enhance clinical results are focused on several main areas including design and detection of more effective carrier molecules, selection of the best gene delivery methods, and detection of novel therapeutic targets. Neurodegenerative diseases such as Alzheimer's disease (AD) are still an important issue for scientists because it is difficult to cure with the available molecular medications and conventional treatments. Due to the complex nature of the brain structures and heterogeneous morphological and physiological properties of neuronal cells, interventions for cerebral-related disorders using surgical approaches, and classical and ongoing treatments remain hard for physicians. Furthermore, the development of newly designed medications attempts to target AD are not successful in improving AD, because abnormalities of tau protein, aggregation of amyloid β (Aβ) peptide, inflammatory responses, etc lead to advanced neurodegeneration processes that conventional treatments cannot stop them. In recent years, novel diagnostic strategies and therapeutic approaches have been developed to identify and cure early pathological events of AD. Accordingly, many gene-based therapies have been developed and introduce the therapeutic potential to prevent and cure AD. On the other hand, genetic investigations and postmortem assessments have detected a large number of factors associated with AD pathology. Also, genetically diverse animal models of AD help us to detect and prioritize novel resilience mechanisms. Hence, gene therapy can be considered an effective and powerful tool to identify and treat human diseases. Ultimately, gene study and gene-based therapy with a critical role in the detection and cure of various human disorders will have a fundamental role in our lives forever. This scientific review paper discusses the present status of different therapeutic strategies, particularly gene-based therapy in treating AD, along with its challenges. [ABSTRACT FROM AUTHOR]

• The theory of shear lag model is extended. • Viscoelastic shear lag model is developed to illustrate the mechanical behavior of axon under transient tensile loading. • The paper explains how the vulnerable axons protect themselves from overall damage over the course of evolution. • The paper explains how axons achieve an outstanding mechanical balance of high stiffness and toughness. Axons with staggered microtubules cross-linked by tau protein possess a remarkable mechanical balance of high specific stiffness and toughness. Owing to their viscoelastic nature, axons exhibit stress rate-dependent mechanical behavior, which is relevant to their selective vulnerability to damage in traumatic brain injury. A Kelvin–Voigt viscoelastic shear lag model is developed to elucidate the mechanical responses of axons under transient tensile force. Analytical closed-form expressions are derived to characterize the relative sliding, stress transfer and failure mechanism between microtubule and tau protein while the axon is stretched transiently. The results from the theoretical solutions elucidate how the MT-tau interface length and stress rate affect the mechanical responses of axon. It is found that axonal failure mechanism may be different under different loading conditions. Long microtubules are more vulnerable to rupture at high stress rate, yet short microtubules are likely to detach from microtubule bundles under large deformations. In the view of multi-level failure of axon, it is illustrated how the vulnerable axons protect themselves from overall damage, and how the axon can simultaneously achieve an outstanding mechanical balance of high specific stiffness and toughness. [ABSTRACT FROM AUTHOR]

Tauopathies are neurodegenerative diseases characterized by abnormal conformational changes in tau protein. Early hyperphosphorylation-induced conformational changes are considered a hallmark of tauopathy, but real-time tracking methods are lacking. Here, we present two novel fluorescence resonance energy transfer (FRET)-based tau biosensors that detect such changes with high spatiotemporal resolution at the single-cell level. The TAUCON biosensor measures instantaneous conformational changes in hyperphosphorylated tau within 20 min, while the TAUCOM biosensor detects changes in the paper-clip structure of microtubule-associated tau. Our biosensors provide faster and more precise detection than conventional methods and can serve as valuable tools for investigating the initial causes, mechanisms, progression, and treatment of tauopathies. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disease that accounts for 70% of all dementia. Early stage diagnosis of AD is essential as there is no certain treatment after the lesion has progressed in the late stage. Nevertheless, there are still limitations of early diagnosis of AD using neuroimaging and psychological memory assessments. Here, we demonstrate ultrasensitive and multiplexed detection of pivotal AD biomarkers (Aβ 1-42 and t-Tau) in biofluids using a reduced graphene oxide field-effect transistor (gFET). The proposed approach provides a wide logarithmically linear range of detection from 10−1–105 pg mL−1 and a femtomolar-level limit of detection in biofluids (human plasma and artificial cerebrospinal fluid) as well as phosphate-buffered saline (PBS). Furthermore, as these core biomarkers have different surface charges in physiological conditions based on the isoelectric point (pI), we achieved a distinctive output signal for each biomarker. The gFET biosensor platform presented in this paper has great potential and can be used for early diagnosis of AD in clinical practice as well as accurate analysis based on the surface charge of the analytes. • The amyloid-β (Aβ) and tau protein in biofluids are pivotal biomarkers for the early stage diagnosis of Alzheimer's disease. • A graphene-based field-effect transistor (gFET) is designed for multiplexed detection of Aβ 1-42 and total tau (t-Tau). • Aβ 1-42 and t-Tau possess different charges owing to their isoelectric point, resulting in distinctive doping effects on gFET. • Femtomolar detection of Aβ 1-42 and total tau (t-Tau) have been achieved in human plasma and artificial cerebrospinal fluid. [ABSTRACT FROM AUTHOR]