The function of the nervous system depends on the formation and maintenance of accurate synaptic connections between neurons and target cells, and proteins at synaptic sites play many complex and important regulatory roles such as controlling membrane excitability, embedding neuronal mediator receptors, maintaining stability of intracellular calcium ions, and preserving the activities of protein kinases and phosphodiesterases. Various environmental factors and stress conditions, such as free calcium ion levels, pH changes, redox processes, ATP and free radical concentrations, and local potential changes, affect the function of proteins in brain tissues, while abnormalities in protein synthesis, degradation, and spatial conformation also diminish the function of proteins, which become critical elements in the occurrence and progression of neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, and motor neuron disease, among others. Alzheimer’s disease (AD), Parkinson’s disease, motor neuron disease, and other neurodegenerative diseases have become critical elements in the development of AD and motor neuron disease, and have attracted increasing attention as valuable targets for neurodegenerative diseases. First described a century ago by the German psychiatrist Alois Alzheimer, Alzheimer’s disease is the most common cause of progressive dementia in the elderly population. Different reports in the literature indicate that about 5% of the elderly population at the age of 65 years stage suffers from Alzheimer’s disease, with the prevalence increasing nearly exponentially with each 5-year increase in age, and even being present in nearly half of the population aged 85 years and above. As a chronic neurodegenerative condition, Alzheimer’s disease leads to progressive impairment of cognitive function, such as memory loss, impaired judgment, lack of logic, disorientation and language decline, as well as behavioral and even personality changes. Although the pathogenesis of Alzheimer’s disease is complex and involves various theories such as cholinergic neurotransmitter deficiency, excitatory amino acid-mediated neurotoxicity, metal (zinc, copper) toxicity, inflammatory response and lipid metabolism abnormality, the characteristic pathological changes of senile plaques and neurofibrillary tangles observed in autopsies of brain tissues from patients with Alzheimer’s disease have led many researchers to focus on protein metabolism abnormalities. in the pathogenesis of Alzheimer’s disease. The senile plaques are extracellular damage to neurons of the nervous system, and it was not until the 1980s that it became known from the cerebral vasculature of patients with Alzheimer’s disease, as well as from purification of the core proteins of the senile plaques and analysis of some of the amino acid sequences, that the core component consists of β-amyloid peptide (Aβ) surrounded by dystrophic neural protrusions, activated microglia, and activated astrocytes. There is overwhelming evidence that the accumulation of β-amyloid (specifically Aβ42 peptide) in brain tissue initiates a cascading series of reactions that ultimately lead to neuronal deficits, neurodegeneration, and the onset of dementia. In fact, Aβ is not just an abnormal or pathological consequence of the metabolic process initially envisioned for APP, but β-amyloid can be detected in plasma and cerebrospinal fluid in normal cell cultures and in healthy populations. overproduction of Aβ, in particular Aβ42, decreased clearance, aggregation and oligomerization, activation of glial cells upon deposition, and synaptic and neuronal damage constitute the main processes underlying the amyloid theory of Alzheimer’s disease. protein doctrine as the main process. Beta amyloid peptides are proteolytic fragments of amyloid precursor protein (APP), normally produced by sequential cleavage by proteases known as α, β, and γ secretases.APP is viewed as a transmembrane-anchored protein structure consisting of a signaling sequence, large extramembranous regions, a single transmembranous domain, and a small intracellular cytosol carboxyl (end) terminus. α Secretases, as components of the metalloproteinase family which is involved in cleavage of the Aβ sequence itself and is not thought to lead to amyloid peptide formation, while experiments have shown that muscarinic acetylcholine receptor agonists stimulate α-secretase activity and reduce Aβ production in cell culture. β-secretase, first identified and cloned in 1999, is a membrane-bound aspartyl protease that cleaves the extrafunctional region of the amyloid precursor protein and contributes to the shedding of the extrafunctional regions of the precursor proteins α and β shedding; γ-secretase ultimately disassembles the structure of the transmembrane domain of the carboxyl (terminal) end of APP, releasing p3 and Aβ to the extracellular as well as releasing the structure of the intracellular domain of APP to the cytosol. Because of this, β and γ secretases play an important role in β amyloid formation in Alzheimer’s disease, and the use of β and γ secretase inhibitors to reduce the level of β amyloid or reduce the formation of β amyloid, to block or delay the onset of neurodegeneration and dementia has become the current choice of drug therapeutic targets, and a large number of preclinical and clinical drug trial studies have been conducted. Patients with early-onset familial Alzheimer’s disease are often thought to be associated with overproduction of β-amyloid due to the APP autosomal and progerin gene variants; however, evidence of β-amyloid overproduction is lacking in more disseminated Alzheimer’s disease patients, suggesting instead that Aβ builds up in the brain tissue of the patients due to decreased β-amyloid clearance. Enzymes known to promote beta amyloid degradation include neprilysin (NEP), insulinolytic enzymes (IDE), matrix metalloproteinases (MMPs), endothelin-converting enzyme (ECE), angiotensin-converting enzyme, fibrinolytic enzymes, and histioblastase (CatB). Some evidence suggests that deficiencies of these enzymes increase Aβ levels, whereas high levels of secretion of these enzymes result in a significant decrease in Aβ levels. The activity of enzymes promoting β-amyloid degradation is closely related to age, e.g., as aging progresses, NEP and IDE are less selective in brain tissue-susceptible structures like the hippocampus and temporal cortex, which are anatomical structures that are also often the first and specific sites of β-amyloid deposition. Conversely, the presence of large amounts of Aβ may in turn activate β-amyloid-degrading enzymes such as MMPs, fibrinolytic enzymes, and CatB, but animal experiments have observed that this phenomenon occurs only in younger, but not older, animals, suggesting the existence of a possible age-related protective mechanism. It is more difficult to increase the activity of β-amyloid-degrading enzymes that can promote β-amyloid degrading enzymes than it is to study protease inhibitors, and some of the enzymes themselves are involved in a number of important physiological functions, e.g., IDE regulates insulin levels to control blood glucose, and NEP modulates cardiac natriuretic peptide levels, which are closely related to blood pressure. β-amyloid-degrading enzymes are affected by a variety of factors, e.g., cholecystokinin may be involved in β-amyloid degrading enzymes by affecting protein inversion and The presence of endogenous β-amyloid-degrading enzyme inhibitors also regulates β-amyloid-degrading enzymes, such as CatB activity is inhibited by cysteine protease inhibitors (CysC), and CysC levels are significantly increased in susceptible neurons and cerebrospinal fluid of patients with Alzheimer’s disease. Simultaneous application of strategies to reduce the overproduction of β-amyloid and to promote the acceleration of its degradation may be expected as a more effective approach in the future treatment of Alzheimer’s disease. As mentioned earlier, β-amyloid can be detected in plasma and cerebrospinal fluid from both normal cell cultures and healthy populations, and laboratory results have hypothesized that β-amyloid peptides may have both neurotrophic and neurotoxic effects, and that their neurotoxicity is partly related to the aggregation state of β-amyloid and the solidification of the Aβ structure. The aging cohesive Aβ is neurotoxic, while the nascent soluble Aβ is not neurotoxic. β-amyloid peptide exerts neurotoxicity when its spatial conformation changes from an α-helical structure (monomer) to an oligomer by β-folding. Preventing oligomerization of small molecules of Aβ and thus toxic effects is another target for therapeutic options in Alzheimer’s disease. Copper and zinc ions may intervene in the aggregation of Aβ, and clinical trials have been conducted using metal chelators such as chloroiodo hydroxyquin. Active or passive immunological approaches to generate antibodies against β-amyloid, thereby reducing Aβ formation and promoting Aβ degradation have confirmed their possibility and effectiveness at the neuropathological and animal experimental level, but the scenario of such effectiveness including the status of improvement of cognitive functioning of the patients in human clinical drug trials, as well as safety considerations arising from immunologic treatments are yet to be or are being observed. Neurofibrillary tangles are another pathological change characteristic of Alzheimer’s disease, of which the hyperphosphorylated microtubule-associated protein tau constitutes a major component. Studies have shown that tau exacerbates brain dysfunction induced by Aβ and excitotoxins, and that even a partial reduction in tau levels can greatly minimize or prevent the deleterious effects of these factors. Therefore, tau has attracted much attention as a candidate therapeutic target not only in Alzheimer’s disease, but also in other neurological disorders involving excitotoxicity, such as stroke and epilepsy. The human tau gene is located on chromosome 17q21 and contains at least 16 exons. selective splicing of mRNAs produces more than six isoforms of tau proteins, and post-translational modifications increase the complexity of these protein isoforms. tau protein is a major microtubule-associated protein, usually found in axons, and is thought to play an initiating and stabilizing role in microtubule assembly, and in pathological states, tau interacts with the cytoskeleton. Under pathological conditions, tau interacts with the cytoskeletal molecule actin, mediating changes in dendritic spine shape as well as synaptic plasticity. At the neurobiochemical level, tau phosphorylation or hyperphosphorylation, although regulated by a variety of factors, is a major component in the maintenance of normal physiological efficacy or in the development of neurological disorders. tau phosphorylation promotes microtubule assembly, whereas aberrant hyperphosphorylation interferes with normal physiological function by decreasing the binding and stabilizing capacity of tau and microtubules, and, conversely, loss of function due to pathologic tau proteins can be reversed by the loss of tau function and the reduction of the ability to bind and stabilize microtubules. On the contrary, loss of function due to pathological tau protein can be restored by dephosphorylation. The imbalance between kinase and phosphatase is the key factor leading to overphosphorylation, and the regulation of kinase and phosphatase activities to reduce tau protein-induced neurodegenerative changes has become a hot research topic with potential clinical applications. The tau protein has more than 30 phosphorylation sites, and a large number of proline- and nonproline-directed kinases have been shown to phosphorylate tau protein in vitro, including glycogen synthase kinase (GSK3-b), cdk5, extracellular signal-regulated kinase-2 (ERK2), microtubule-affinity-regulated kinase (MARK), protein kinase A (PKA), stress-activated protein kinase (SAPK), SAPK, and other kinases. SAPK) family, Ca2+/calcium-regulated protein-dependent kinase II and casein kinases I and II. It has been found that overexpression and enhanced activity of these enzymes cause tau proteins to become highly phosphorylated and aggregated, which in turn leads to the onset of neuronal deafferentation and neurodegeneration. Inhibition of the activity of these enzymes, such as the application of lithium can inhibit GSK3 and reduce the overphosphorylation of tau proteins and decrease the level of aggregated insoluble tau proteins. The tau protein phosphatase activity was significantly decreased in the brains of patients with Alzheimer’s disease compared to controls. The protein phosphatases PP2A, PP2B, and to a lesser extent PP1 are involved in the regulation of tau protein phosphorylation, and therefore, in addition to inhibiting kinase activity, restoring or up-regulating tau protein phosphatase activity also inhibits tau protein over-phosphorylation.The NMDA receptor antagonist, Memantine, has achieved a certain degree of efficacy in the treatment of patients with moderate to severe Alzheimer’s disease. One of the possible mechanisms lies in the restoration of PP2A enzyme activity through the PP2A signaling pathway. In addition, similar to β-amyloid, soluble tau proteins are not cytotoxic, but only when overgenerated tau protein fragments form an aggregated state, and the use of tau protein aggregation inhibition is thought to reduce the neurotoxicity of abnormally over-phosphorylated tau proteins.