Journal of Translational Neurosciences

Description

Cognitive functions gradually deteriorate in Alzheimer's disease (AD), an age-related neurodegenerative condition. Amyloid plaque deposits in the extracellular environment and tau protein tangles in the neurofibrillary system within the cell are the pathological hallmarks. Synaptic dysfunction and deficiencies in neurochemicals are thought to be the causes of the observed cognitive deficits. During progressive aging, a number of neurochemical abnormalities have been observed, and these abnormalities are linked to cognitive problems in the sporadic form of AD. One of the main approaches taken to treat AD is acetylcholinesterase inhibitor therapy. Preclinical studies and clinical development of a variety of new AD treatment strategies have demonstrated positive effects over the past decade. The purpose of this review is to talk about the neurobiology of AD, the connection between neurochemical abnormalities and cognitive decline, and new ways to treat AD. Around 7.7 million new cases of dementia are reported each year. Loss of cholinergic neurons, extracellular deposition of -amyloid (A) protein as a result of abnormal processing of Amyloid Precursor Protein (APP), formation of hyperphosphorylated tau protein in intracellular Neurofibrillary Tangles (NFT), gliosis, and loss of neurons are all pathological features of AD.

Multi-Target Directed Ligand Theory

 In addition, it is well established that oxidative stress, excitotoxicity, neuro-inflammation, neurotransmitter deficiencies, and intracellular tau tangle formation play a significant role. Acetylcholine (ACh), produced by cholinergic neurons, is essential for memory and learning. Loss of cholinergic neurons in both the cortical and hippocampal regions has been identified as a hallmark of AD. Additionally, it has been reported that serotonergic, glutamatergic, dopaminergic, and adrenergic neurons are altered in AD. In clinical settings, only Acetylcholinesterase Inhibitors (AChEIs) like donepezil, rivastigmine, galantamine, and huperzine and N-methyl-D-aspartate (NMDA) receptor antagonists like -memantine have been used to alleviate AD symptoms. However, the neurodegenerative processes could not be stopped or slowed down by these agents. For the treatment of AD, a number of new therapeutic approaches that have demonstrated positive effects over the past decade are currently in clinical development. It has been reported that the Multi-Target Directed (MTD) ligand, one of the most significant revolutionary approaches in the drug design strategy, offers new hope for the treatment of multifactorial diseases like Alzheimer's disease. This is because the one molecule, one target, directed ligand strategy of traditional drug design, which was found to be ineffective in treating multifactorial diseases like AD, is to blame. Based on the multi-target directed ligand theory, a memantine heterodimer, specifically the 7-methoxytacrine molecule, has been investigated for the treatment of AD.

Fundamental Roles in the Pathogenesis of Ad

The key cytoplasmic organelles that determine life and death are called mitochondria. Mitochondria play a crucial role in aging and the majority of human diseases, including cancer, diabetes, obesity, infertility, hypertension, kidney disease, and neurodegenerative diseases like Alzheimer's, Parkinson's, multiple sclerosis, Huntington's, Amyotrophic Lateral Sclerosis (ALS), and Freidreich ataxia, according to extensive evidence from clinical studies, postmortem brains, and animal studies. The body's primary source of energy and biomaterials necessary for life's maintenance is glucose metabolism. Mitochondria are necessary for the breakdown of glucose, which kicks off a series of processes that eventually result in the formation of ATP. The human cerebrum depends solely on glucose digestion with neurons in the grown-up mind having the most elevated energy request consuming generally 20% of glucose-determined energy. The brain needs glucose the most because it is the body's primary glucose consumer. Alzheimer's disease is a progressive mental illness that does not have a cure. Due to the progressive loss of neurons in the brain, Alzheimer's disease (AD) is a prevalent debilitating disease characterized by impaired cognitive function. Damaged mitochondria likely play fundamental roles in the pathogenesis of AD, according to decades of intensive research.