<p>OBJECTIVETo observe the influence of H102 on the expression of amyloid protein and amyloid precursor protein in the hippocampus of APP695 transgenic mice.p><p>METHODSThe 9-month-old APP695 transgenic mice were randomly divided into the model group and the H102 group; C57BL/6J mice were adopted as normal control group. The H102 group were injected with H102 in a dose of 3 microl/per mouse in lateral ventricle, once a day, for ten days; while the model group and the control group were injected with saline. The hippocampus and temporal cortex of the brain sections from transgenic mice and wild type female mice were subjected to immunohistochemistry and Congo red histological staining, and observed the difference of the protein expression under microscope. The expression of the APP protein was detected by Western blot.p><p>RESULTSAbeta and APP immunohistochemistry showed density of positive cell in the CA1 region of hippocampus of control group were less than model group. H102 peptide reduced the area, and density of positive cells. Congo red staining showed there were lots of amyloid plagues in the brains of model mice but not in the brains of normal control. And the Western blot showed the content of the APP protein of the model group was much higher than the H102 group. H102 significantly decreased the amyloid plagues.p><p>CONCLUSIONThe expression of APP, Abeta are increased in APP695 transgenic mice, and H102 can decrease the level of APP, Abeta in transgenic mice.p>
Amyloid beta-Protein Precursor ; metabolism ; Amyloidogenic Proteins ; metabolism ; Animals ; Brain ; metabolism ; Female ; Gene Expression ; Hippocampus ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic

Converging lines of evidence suggest that cell-to-cell transmission and the self-propagation of pathogenic amyloidogenic proteins play a central role in the initiation and the progression of several neurodegenerative disorders. This "prion-like" hypothesis has been recently reported for alpha-synuclein, a presynaptic protein implicated in the pathogenesis of Parkinson's disease (PD) and related disorders. This review summarizes recent findings on alpha-synuclein prion-like propagation, focusing on its transmission, seeding and degradation and discusses some key questions that remain to be explored. Understanding how alpha-synuclein exits cells and propagates from one brain region to another will lead to the development of new therapeutic strategies for the treatment of PD, aiming at slowing or stopping the disease progression.
alpha-Synuclein* ; Amyloidogenic Proteins ; Brain ; Disease Progression ; Neurodegenerative Diseases ; Parkinson Disease

The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither do we know its consequence. Here, we used SARS-CoV-2 to infect mammalian cells and observed the incorporation of N protein into SGs, which resulted in markedly impaired self-disassembly but stimulated cell cellular clearance of SGs. NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific transient interactions, which not only expedites the phase transition of these proteins to aberrant amyloid aggregation in vitro, but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells. In addition, we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells. Our work indicates that SARS-CoV-2 infection can impair the disassembly of host SGs and promote the aggregation of SG-related amyloid proteins, which may lead to an increased risk of neurodegeneration.
Amyloidogenic Proteins/metabolism* ; Amyotrophic Lateral Sclerosis/genetics* ; Animals ; COVID-19 ; Cytoplasmic Granules/metabolism* ; Mammals ; SARS-CoV-2 ; Stress Granules

Amyloidosis results from the deposition of insoluble, fibrous amyloid proteins, nearly always in the extracellular spaces of organs and tissues. There are several varieties of amyloidosis, each of which is identified by the immunochemical nature of amyloid protein fibrils. Amyloid goiter is a very rare clinical entity and can be confused with a neoplasm. We have experienced a case of amyloid goiter with hypothyroidism secondary to tuberculosis. A 20 years old women with 5 months history of pulmonary tuberculosis was admitted with complaints of diarrhea, abdominal pain, weight loss at one year ago. She had a non-tender, diffuse and firm goiter. Also she had normal thyroid function at the first admission but was found to be hypothyroid at the second admission, 10 months later. Histologic examination revealed amyloid deposition in thyroid gland, stomach, colon and rectum.
Abdominal Pain ; Amyloid* ; Amyloidogenic Proteins ; Amyloidosis ; Colon ; Diarrhea ; Extracellular Space ; Female ; Goiter* ; Humans ; Hypothyroidism* ; Plaque, Amyloid ; Rectum ; Stomach ; Thyroid Gland ; Tuberculosis ; Tuberculosis, Pulmonary ; Weight Loss ; Young Adult

Secondary amyloidosis is characterized by accumulation of insoluble, fibrous amyloid proteins in various tissues and organs, accompanied by infectious or inflammatory diseases. Amyloidosis may involve the thyroid, gastrointestinal tract, kidneys, liver, or bone marrow. Amyloidosis as a complication of Crohn's disease is rare but serious, and may worsen the prognosis. We have experienced a case of amyloid goiter and gastrointestinal amyloidosis secondary to Crohn's disease. A 74-year-old female patient with Crohn's disease was admitted to Soonchunhyang University Hospital with general weakness and poor oral intake. Anterior-neck diffuse goiter and tenderness around the navel were found. Amyloid goiter and gastrointestinal amyloidosis diagnosed by sonoguided needle biopsy of the thyroid and endoscopic biopsies of the stomach and duodenum.
Aged ; Amyloid ; Amyloidogenic Proteins ; Amyloidosis* ; Biopsy ; Biopsy, Needle ; Bone Marrow ; Congo Red ; Crohn Disease* ; Duodenum ; Female ; Gastrointestinal Tract ; Goiter* ; Humans ; Kidney ; Liver ; Prognosis ; Stomach ; Thyroid Gland

Amyloidosis is a disease characterized by the deposition of non-soluble fibrous protein in multiple tissues with a number of possible causes. This protein deposition can occur in any tissue, yet is most commonly seen in kidneys, heart, and gastrointestinal tracts. However, invasion to bone tissues is not often reported. The deposition of amyloid proteins in bone tissues may result in joint pain and pathological fractures; it is important to elucidate the causes and detect early to determine prognosis and treat optimally. In the present case report, with relevant literature review, the authors report a case of total hip arthroplasty in an amyloidosis patient.
Amyloid* ; Amyloidogenic Proteins ; Amyloidosis ; Arthralgia ; Arthroplasty, Replacement, Hip ; Bone and Bones ; Fractures, Spontaneous ; Gastrointestinal Tract ; Heart ; Hip Joint* ; Hip* ; Humans ; Kidney ; Multiple Myeloma* ; Prognosis

<p>OBJECTIVETo investigate the impact of sub-chronic Aluminium-maltolate [Al(mal)3] exposure on the catabolism of amyloid precursor protein (APP) in rats.p><p>METHODSForty adult male Sprague-Dawley (SD) rats were randomly divided into five groups: the control group, the maltolate group (7.56 mg/kg BW), and the Al(mal)3 groups (0.27, 0.54, and 1.08 mg/kg BW, respectively). Control rats were administered with 0.9% normal saline through intraperitoneal (i.p.) injection. Maltolate and Al(mal)3 were administered to the rats also through i.p. injections. Administration was conducted daily for two months. Rat neural behavior was examined using open field tests (OFT). And the protein expressions and their mRNAs transcription related with APP catabolism were studied using enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR).p><p>RESULTSThe expressions of APP, &beta;-site APP cleaving enzyme 1 (BACE1) and presenilin-1 (PS1) proteins and their mRNAs transcription increased gradually with the increase of Al(mal)3 doses (P<0.05). The enzyme activity of BACE1 in the 0.54 and 1.08 mg/kg Al(mal)3 groups increased significantly (P<0.05). The expression of &beta;-amyloid protein (A&beta;) 1-40 gradually decreased while the protein expression of A&beta;1-42 increased gradually with the increase of Al(mal)3 doses (P<0.05).p><p>CONCLUSIONResult from our study suggested that one of the possible mechanisms that Al(mal)3 can cause neurotoxicity is that Al(mal)3 can increase the generation of A&beta;1-42 by facilitating the expressions of APP, &beta;-, and γ-secretase.p>
Amyloidogenic Proteins ; genetics ; metabolism ; Animals ; Drug Administration Schedule ; Environmental Pollutants ; administration & dosage ; toxicity ; Gene Expression Regulation ; drug effects ; Male ; Organometallic Compounds ; administration & dosage ; toxicity ; Pyrones ; administration & dosage ; toxicity ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Esophagogastroduodenoscopy for cancer screening was performed in a 55-year-old woman as part of a health screening program, and revealed a depressed lesion approximately 20 mm in diameter in the lesser curvature of the mid-gastric body. Several biopsy specimens were collected as the lesion resembled early gastric cancer; however, histopathologic evaluation revealed chronic active gastritis with an ulcer and amorphous eosinophilic material deposition. Congo red staining identified amyloid proteins, and apple-green birefringence was shown using polarized light microscopy. Immunohistochemical staining revealed the presence of kappa and lambda chain-positive plasma cells. There was no evidence of underlying plasma cell dyscrasia or amyloid deposition in other segments of the gastrointestinal tract. Echocardiography and computed tomography of the chest, abdomen, and pelvis did not show any significant findings. Thus, the patient was diagnosed with localized gastric amyloidosis with kappa and lambda light chain coexpression.
Abdomen ; Amyloidogenic Proteins ; Amyloidosis* ; Biopsy ; Birefringence ; Congo Red ; Early Detection of Cancer ; Echocardiography ; Endoscopy, Digestive System ; Eosinophils ; Female ; Gastritis ; Gastrointestinal Tract ; Humans ; Mass Screening ; Microscopy, Polarization ; Middle Aged ; Paraproteinemias ; Pelvis ; Plaque, Amyloid ; Plasma Cells ; Stomach Neoplasms ; Thorax ; Ulcer

Alzheimer's disease (AD) is characterized pathologically by cholinergic deficits, extracelluar amyloid deposit, intra-neuronal neurofibrillary tangles, gliosis and neuronal and synaptic loss. The primary therapeutic approach has been cholinergic augumentation by chlolinesterase inhibitors, which at best modestly improve cognitive function. Several recent advances have provided new insights and possibilities in defining therapeutic targets for AD. Research on the underlying pathophysiological dysfunction finally disclose more disease specific processes. Of particular importance is the identification and characterization of the secretases involved in endoproteolytic processing of beta-amyloid precursor protein, the precursor of the amyloid beta-peptide (A beta). It is generally accepted that A beta has pivotal role in the pathogenesis of AD, and that reducing brain A beta levels may be a disease modifying strategy. By inhibiting one or both amyloidogenic secretase and immunization with A beta, neuropathological features of AD can be prevented or alleviated.
Alzheimer Disease* ; Amyloid beta-Peptides ; Amyloid Precursor Protein Secretases ; Brain ; Gliosis ; Immunization ; Neurofibrillary Tangles ; Neurons ; Plaque, Amyloid ; Presenilins

Extracellular accumulation of amyloid beta protein (Abeta) plays a central role in Alzheimer's disease (AD). Some metals, such as copper, lead, and aluminum can affect the Abeta accumulation in the brain. However, the effect of mercury on Abeta accumulation in the brain is not clear. Thus, this study was proposed to estimate whether mercury concentration affects Abeta accumulation in PC12 cells. We treated 10, 100, and 1000 nM HgCl2 (Hg) or CH3HgCl2 (MeHg) for 48 hr in PC12 cells. After treatment, Abeta40 in culture medium increased in a dose- and time-dependent manner. Hg and MeHg increased amyloid precursor protein (APP), which is related to Abeta production. Neprilysin (NEP) levels in PC12 cells were decreased by Hg and MeHg treatment. These results suggested that Hg induced Abeta accumulation through APP overproduction and reduction of NEP.
Aluminum ; Alzheimer Disease ; Amyloid beta-Peptides ; Amyloid Precursor Protein Secretases ; Amyloid* ; Animals ; Brain ; Copper ; Mercuric Chloride ; Metals ; Neprilysin ; PC12 Cells*