The pathogenesis and treatment of Alzheimer's disease (AD) have developed into the frontier with the aging of people in the world. Meanwhile, they are the most difficult steps in the research on this degenerative disease of the nervous system. The over-deposition of beta-amyloid protein in nervous system is the most important feature. The formation and influencing factors of beta-amyloid protein are summarized in this paper. Furthermore, the methods and advance in treatment of AD are reviewed especially.
Aged ; Alzheimer Disease ; drug therapy ; metabolism ; Amyloid beta-Peptides ; metabolism ; Brain ; metabolism ; Humans ; Middle Aged

The injury of exogenous formaldehyde and its merchanism have attracted wide attention from researchers. The latest study found that mammals have a whole system for generating and clearning formaldehyde. However, the imbalance on the system for generating and clearning formaldehyde for various reasons will cause abnormal accumulation of endogenous formaldehyde in vivo, which is closely related to learning diability and memory dysfunction. The increase in endogenous formaldehyde concentration may be one of factors inducing such neurodegenerative diseases as Alzheimer's disease. The study on the relationship between endogenous formaldehyde and such neurodegenerative diseases as Alzheimer's disease is of great significance and can provide new thoughts for preventing and treating Alzheimer's disease with traditional Chinese medicines.
Alzheimer Disease ; drug therapy ; metabolism ; pathology ; Animals ; Drugs, Chinese Herbal ; therapeutic use ; Formaldehyde ; metabolism ; Humans

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases among the elderly and it accounts for nearly 80% of all dementias. The pathogenesis of AD is complicated and enigmatic thus far. The mitochondrial cascade hypothesis assumes that mitochondrial damage may mediate, drive, or contribute to a variety of AD pathologies and may be the main factor in late-onset AD. Currently, there are no widely recognized drugs able to attenuate mitochondrial damage in AD. Notably, increasing evidence supports the efficacy of acupuncture for improving the mitochondrial structure and protecting mitochondrial functions in AD. This review reports the mechanisms by which acupuncture regulates mitochondrial dynamics, energy metabolism, calcium homeostasis and apoptosis. In conclusion, these findings suggest that AD mitochondrial dysfunction represents a reasonable therapeutic target and acupuncture could play a significant role in preventing and treating AD.
Acupuncture Therapy ; Aged ; Alzheimer Disease/drug therapy* ; Apoptosis ; Humans ; Mitochondria/metabolism*

The pathogenesis and treatments based on meridian differentiation of senile dementia are discussed through analyses and researches on the theory of "cerebral collaterals injury by toxins" and "collateral diseases". The symptoms of "Cerebral collaterals injury by toxins" are preliminary characterized by toxins and blood stasis occluding brain collaterals. "Cerebral collateral injury by toxins" and "Governor Vessel occlusion by blood stasis" are taken as the major pathogeneses of senile dementia. And the treatment should be focused on clearing the collaterals. Clearance acting as reinforcing as well as to clear and modify the Governor Vessel are taken as crucial sections in the treatment of senile dementia based on meridian differentiation. It is also the application of acupuncture-moxibustion intervention in senile dementia based on the theory of "cerebral collateral injury by toxins", which expands the application of the theory concerning "collateral diseases" in disease prevention and treatment with acupuncture-moxibustion.
Acupuncture Therapy ; Alzheimer Disease ; diagnosis ; metabolism ; therapy ; Brain ; drug effects ; metabolism ; Diagnosis, Differential ; Humans ; Meridians ; Toxins, Biological ; metabolism ; pharmacology

Review the research and development status that acupuncture and Chinese medicine are treating Alzheimer disease (AD) for recent year. From pathogenesy of AD view explain the interventional effects and mechanisms of traditional Chinese medicine on Alzheimer disease. Summarize the main species of Chinese medicine compound and components playing roles. Prefer that traditional Chinese medicine has multiple effects and this will be the development direction of it on Alzheimer disease.
Alzheimer Disease ; drug therapy ; metabolism ; pathology ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; methods

OBJECTIVETo observe the effect of ginsenoside Rg1 on the expressions of phosphory protein Tau (P-Tau) and caspase-3 in brain slices from AD model rats.

METHODThe brains of 5-week-old Wista rats were cut into slices which were 400 microm thick. These brain slices were divided into five groups: normal contral group, untreated group, low-dose, medium-dose and high-dose ginsenoside Rg1 groups (60, 120, 240 micromol x L(-1)). And there were 10 slices in each group. These brain slices were cultured with artificial cerebrospinal fluid. After the brain slices in ginsenoside Rg1 groups were administration with ginsenoside Rg1 for 2 h preventively, brain slices in untreated group and ginsenoside Rg1 groups were administrated with okadaic acid (OA) for 3 h to induce hyperphosphorylation of Tau protein to prepare AD models. And the effects of ginsenoside Rg1 on the expressions of P-Tau and caspase-3 in brain slices from AD model rats in each group were observed with immunohistochemistry and image analysis technology.

RESULTThe levels of the expressions of P-Tau and caspase-3 in the untreated group were significantly higher than those in the normal control group (P < 0.01). Compared with untreated group, the levels of the expressions of P-Tau and caspase-3 in ginsenoside Rg1 groups were significantly low (P < 0.01 or P < 0.05).

CONCLUSIONGinsenoside Rg1 could inhibit the expression of P-Tau to slow the formation of neurofibrillary tangles and could inhibit the expression of caspase-3 to inhibit neuronal apoptosis to protect the nerve cells, so as to play the role of anti-dementia.

Alzheimer Disease ; drug therapy ; metabolism ; Animals ; Brain ; drug effects ; metabolism ; Caspase 3 ; metabolism ; Disease Models, Animal ; Ginsenosides ; therapeutic use ; Immunohistochemistry ; Male ; Rats ; Rats, Wistar ; tau Proteins ; metabolism

Mammalian cells remove misfolded proteins using various proteolytic systems, including the ubiquitin (Ub)-proteasome system (UPS), chaperone mediated autophagy (CMA) and macroautophagy. The majority of misfolded proteins are degraded by the UPS, in which Ub-conjugated substrates are deubiquitinated, unfolded and cleaved into small peptides when passing through the narrow chamber of the proteasome. The substrates that expose a specific degradation signal, the KFERQ sequence motif, can be delivered to and degraded in lysosomes via the CMA. Aggregation-prone substrates resistant to both the UPS and the CMA can be degraded by macroautophagy, in which cargoes are segregated into autophagosomes before degradation by lysosomal hydrolases. Although most misfolded and aggregated proteins in the human proteome can be degraded by cellular protein quality control, some native and mutant proteins prone to aggregation into beta-sheet-enriched oligomers are resistant to all known proteolytic pathways and can thus grow into inclusion bodies or extracellular plaques. The accumulation of protease-resistant misfolded and aggregated proteins is a common mechanism underlying protein misfolding disorders, including neurodegenerative diseases such as Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease (PD), prion diseases and Amyotrophic Lateral Sclerosis (ALS). In this review, we provide an overview of the proteolytic pathways in neurons, with an emphasis on the UPS, CMA and macroautophagy, and discuss the role of protein quality control in the degradation of pathogenic proteins in neurodegenerative diseases. Additionally, we examine existing putative therapeutic strategies to efficiently remove cytotoxic proteins from degenerating neurons.
Alzheimer Disease/drug therapy/metabolism ; Amyloid beta-Peptides/metabolism ; Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; Animals ; Autophagy/drug effects ; DNA-Binding Proteins/metabolism ; Humans ; Huntington Disease/drug therapy/genetics/metabolism ; Lysosomes/metabolism ; Molecular Targeted Therapy ; Mutation ; Nerve Tissue Proteins/genetics/metabolism ; Neurodegenerative Diseases/drug therapy/*metabolism ; Parkinson Disease/drug therapy/metabolism ; PrPSc Proteins/metabolism ; Prion Diseases/drug therapy/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Proteolysis ; Proteostasis Deficiencies/metabolism ; Superoxide Dismutase/metabolism ; Ubiquitin/metabolism ; alpha-Synuclein/metabolism ; tau Proteins/metabolism

AIMA method of stereotaxic apparatus was employed to damage the nucleus basalis of Meynert, and the effects of Tiao-xinzishen prescriptions on neurotransmitters such as ACh, 5-HT and NE in hippocampus were observed.

METHODSRats were placed on the brain stereotaxic apparatus and received a bilateral lesion of Meynert by IA injection, according to the atlas of Daxinos and Watson. After seven days of lesion, AD rats were selected. Rats were treated with Tiaoxin or/and Zishen prescription for 20 days, respectively. Hippocampus ACh was measured by spectrophotometer and 5-HT and NE by high performance liquid chromatography (HPLC).

RESULTSThe contents of hippocampus ACh, 5-HT and NE of AD rats were significantly increased after the treatment with the three prescriptions, respectively.

CONCLUSIONThese prescriptions had some up regulating effects on hippocampus neurotransmitters in rats, which had already decreased due to dementia.

Alzheimer Disease ; drug therapy ; metabolism ; Animals ; Drugs, Chinese Herbal ; therapeutic use ; Hippocampus ; metabolism ; Male ; Neurotransmitter Agents ; metabolism ; Phytotherapy ; Rats ; Rats, Wistar ; Serotonin ; metabolism

Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors that includes obesity, diabetes, and dyslipidemia. Accumulating evidence implies that MetS contributes to the development and progression of Alzheimer's disease (AD); however, the factors connecting this association have not been determined. Insulin resistance (IR) is at the core of MetS and likely represent the key link between MetS and AD. In the central nervous system, insulin plays key roles in learning and memory, and AD patients exhibit impaired insulin signaling that is similar to that observed in MetS. As we face an alarming increase in obesity and T2D in all age groups, understanding the relationship between MetS and AD is vital for the identification of potential therapeutic targets. Recently, several diabetes therapies that enhance insulin signaling are being tested for a potential therapeutic benefit in AD and dementia. In this review, we will discuss MetS as a risk factor for AD, focusing on IR and the recent progress and future directions of insulin-based therapies.
Alzheimer Disease/etiology/metabolism ; Amyloid beta-Peptides/metabolism ; Animals ; Brain/metabolism ; Cognition Disorders/*etiology/*metabolism ; Humans ; Insulin/metabolism ; *Insulin Resistance ; Metabolic Syndrome X/complications/drug therapy/*metabolism ; Molecular Targeted Therapy ; Signal Transduction/drug effects ; tau Proteins/metabolism

Because of the proposed importance of mitochondrial cytochrome C oxidase (COX) decrease in Alzheimer's disease (AD) , the protective effect of Shenwu capsule on mitochondrial deficiency model rats and its pharmacological mechanism were investigated in present study. Rats were administered with azide at 1 mg . kg-1 . h-1 subcutaneously via an Alzet minipump for 30 days. Tweny-four hours after the operation, the rats were administered intragastrically by Shenwu capsule with the dose of 0. 45, 0. 9 and 1. 8 g . kg-1 . d-1 for one month. Then learning-memory ability was determined by the watermaze test and passive avoidance tests. The activity of choline-acetyl-transfertase(ChAT) and acetylcholinesterase (AChE) in hippocampus and cortex of rats were measured by radiochemical method and hydroxylamine colorimetry separately. M-cholinergic receptor binding ability (M-binding) was assayed by radio binding. Chronic infusion of sodium azide via minipump induced learning-memory deficiency of rats. Both ChAT activity and M-binding decreased in hippocampus and cortex of model rats, however, the activity of AChE increased in hippocampus and was not affected at the cortex. As the result, the cholinergic function of the brain decreased in model rats. Shenwu capsule significantly improved learning and memory ability and the mechanism may be related with the improved cholinergic function in model brain: ChAT activity and M-binding significantly increased in Shenwu treated groups compared with model group; and the increased activity of AChE in hippocampus returned to normal. Mitochondria, especially mitochondrial cytochrome C oxidase, may play the key role in the early event of AD. Chronic, partial in vivo inhibition of mitochondrial cytochrome C oxidase in rats provides a suitable model mimicking several aspects of AD. Shenwu capsule indicate effectiveness in AD-like mitochondrial deficiency model rats, so it would be applied in the treatment of AD.
Acetylcholinesterase ; metabolism ; Alzheimer Disease ; drug therapy ; Animals ; Brain ; drug effects ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Electron Transport Complex IV ; metabolism ; Learning ; drug effects ; Memory ; drug effects ; Mitochondria ; drug effects ; metabolism ; Rats