ABSTRACT
Alzheimer's disease is a fatal chronic neurodegenerative condition marked by a gradual decline in cognitive abilities and impaired vascular function within the central nervous system. This affliction initiates its insidious progression with the accumulation of two aberrant protein entities including Aß plaques and neurofibrillary tangles. These chronic elements target distinct brain regions, steadily erasing the functionality of the hippocampus and triggering the erosion of memory and neuronal integrity. Several assumptions are anticipated for AD as genetic alterations, the occurrence of Aß plaques, altered processing of amyloid precursor protein, mitochondrial damage, and discrepancy of neurotropic factors. In addition to Aß oligomers, the deposition of tau hyper-phosphorylates also plays an indispensable part in AD etiology. The brain comprises a complex network of capillaries that is crucial for maintaining proper function. Tau is expressed in cerebral blood vessels, where it helps to regulate blood flow and sustain the blood-brain barrier's integrity. In AD, tau pathology can disrupt cerebral blood supply and deteriorate the BBB, leading to neuronal neurodegeneration. Neuroinflammation, deficits in the microvasculature and endothelial functions, and Aß deposition are characteristically detected in the initial phases of AD. These variations trigger neuronal malfunction and cognitive impairment. Intracellular tau accumulation in microglia and astrocytes triggers deleterious effects on the integrity of endothelium and cerebral blood supply resulting in further advancement of the ailment and cerebral instability. In this review, we will discuss the impact of tau on neurovascular impairment, mitochondrial dysfunction, oxidative stress, and the role of hyperphosphorylated tau in neuron excitotoxicity and inflammation.
ABSTRACT
TRP (Transient receptor potential) channels are integral membrane proteins consisting of a superfamily of cation channels that allow permeability of both monovalent and divalent cations. TRP channels are subdivided into six subfamilies: TRPC, TRPV, TRPM, TRPP, TRPML, and TRPA, and are expressed in almost every cell and tissue. TRPs play an instrumental role in the regulation of various physiological processes. TRP channels are extensively represented in brain tissues and are present in both prokaryotes and eukaryotes, exhibiting responses to several mechanisms, including physical, chemical, and thermal stimuli. TRP channels are involved in the perturbation of Ca2+ homeostasis in intracellular calcium stores, both in neuronal and non-neuronal cells, and its discrepancy leads to several neuronal disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic lateral sclerosis (ALS). TRPs participate in neurite outgrowth, receptor signaling, and excitotoxic cell death in the central nervous system. Understanding the mechanism of TRP channels in neurodegenerative diseases may extend to developing novel therapies. Thus, this review articulates TRP channels' physiological and pathological role in exploring new therapeutic interventions in neurodegenerative diseases.
ABSTRACT
This decade has seen the beginning of ground-breaking conceptual shifts in the research of Alzheimer's disease (AD), which acknowledges risk elements and the evolving wide spectrum of complicated underlying pathophysiology among the range of diverse neurodegenerative diseases. Significant improvements in diagnosis, treatments, and mitigation of AD are likely to result from the development and application of a comprehensive approach to precision medicine (PM), as is the case with several other diseases. This strategy will probably be based on the achievements made in more sophisticated research areas, including cancer. PM will require the direct integration of neurology, neuroscience, and psychiatry into a paradigm of the healthcare field that turns away from the isolated method. PM is biomarker-guided treatment at a systems level that incorporates findings of the thorough pathophysiology of neurodegenerative disorders as well as methodological developments. Comprehensive examination and categorization of interrelated and convergent disease processes, an explanation of the genomic and epigenetic drivers, a description of the spatial and temporal paths of natural history, biological markers, and risk markers, as well as aspects about the regulation, and the ethical, governmental, and sociocultural repercussions of findings at a subclinical level all require clarification and realistic execution. Advances toward a comprehensive systems-based approach to PM may finally usher in a new era of scientific and technical achievement that will help to end the complications of AD.
ABSTRACT
Alzheimer's disease (AD) is a neurodegenerative disorder with no clear causative event making the disease difficult to diagnose and treat. The pathological hallmarks of AD include amyloid plaques, neurofibrillary tangles, and widespread neuronal loss. Amyloid-beta has been extensively studied and targeted to develop an effective disease-modifying therapy, but the success rate in clinical practice is minimal. Recently, neuroinflammation has been focused on as the event in AD progression to be targeted for therapies. Various mechanistic pathways including cytokines and chemokines, complement system, oxidative stress, and cyclooxygenase pathways are linked to neuroinflammation in the AD brain. Many cells including microglia, astrocytes, and oligodendrocytes work together to protect the brain from injury. This review is focused to better understand the AD inflammatory and immunoregulatory processes to develop novel anti-inflammatory drugs to slow down the progression of AD.
