Biomedical subjects

Min Zhu

Publications and source records attributed to Min Zhu.

At least 55 records · Page 3Linked to original sources

PubMed2005

Multipotential differentiation of adipose tissue-derived stem cells.

Tissue engineering offers considerable promise in the repair or replacement of diseased and/or damaged tissues. The cellular component of this regenerative approach will play a key role in bringing these tissue engineered constructs from the laboratory bench to the clinical bedside. However, the ideal source of cells still remains unclear and may differ depending upon the application. Current research for many applications is focused on the use of adult stem cells. The properties of adult stem cells that make them well-suited for regenerative medicine are (1) ease of harvest for autologous transplantation, (2) high proliferation rates for ex vivo expansion and (3) multilineage differentiation capacity. This review will highlight the use of adipose tissue as a reservoir of adult stem cells and draw conclusions based upon comparisons with bone marrow stromal cells.

Adipose Tissue↗

PubMed2005

[Study on NB4 cell apoptosis induced by trichosanthin].

In order to study the influence of trichosanthin (TCS) on apoptosis and growth inhibition of human NB4 cells in vitro, the expression of annexin V and the change of DeltaPsim of NB4 cells induced by TCS was analyzed by FACS, and MTT assay was adopted to measure the growth inhibition ratio of NB4 cells treated with TCS. Apoptosis was assayed by agarose gel electrophoresis. The results showed the higher concentration of TCS and the longer the acting time, the stronger growth inhibition of NB4 cells. The expression of annexin V was positive, and the positive ratio was greatly enhanced with prolongation of acting time. DeltaPsim reduced gradually while the apoptosis cells increasing. DNA agarose gel electrophoresis showed a gradient, which confirmed that TCS could induce NB4 cells apoptosis. In conclusion, taken together, data show that TCS can inhibit NB4 growth in vitro, and induce apoptosis. Experiment provides an important evidence for application of TCS in clinical treatment of acute promyelocytic leukemia.

Antineoplastic Agents, Phytogenic↗

PubMed2005

[Study of relations between matrix metalloproteinase-9 polymorphism (C-1562T) and acute coronary syndrome in Han population of China].

OBJECTIVE: To investigate the association between acute coronary syndrome (ACS) and functional matrix metalloproteinase-9 polymorphism (C-1562-T). METHODS: This study was conducted with a case-control design including 101 patients with angiographically documented ACS and 105 control subjects who were free from coronary artery disease and had normal angiograms. Genotype was determined by polymerase chain reaction-restriction fragment length polymorphism for the common C-1562-T functional promoter polymorphism of the MMP-9 gene.The relationship between the polymorphism in the MMP-9 gene and the severity of coronary arterial stenosis was analyzed. RESULTS: The results of individual polymorphisms analysis showed that the frequency of C/T and T/T genotypes of the C-1562-T polymorphism (27.2%) in patients with ACS was significantly higher than that in those with a normal angiogram (13.34%).The frequencies of -1562T allele were 14.9% and 7.2% in ACS group and control group respectively (Chi2 = 5.617, P = 0.018). The frequencies of C/T and T/T genotypes of the C-1562-T polymorphism were not statistically different among ACS patients with normal and one,two,three or more significantly diseased vessels (Chi2 = 0.601, P = 0.896). CONCLUSION: The present findings suggest that the genetic polymorphism in MMP-9 promoter (C-1562-T) is associated with the susceptibility to ACS in the Han population of China. And the C-1562-T polymorphism may not be useful as a predictor of the severity of coronary atherosclerosis.

Acute Coronary Syndrome↗

PubMed2005

[Study on platelet activated state and platelet activated function in adults with acute leukemia].

To investigate the changes of platelet activated state and platelet activated function by trace whole blood flow cytometry (FCM), and to explore the mechanism of hemorrhage and infiltration in adults with acute leukemia, the expression percentage and changes of these expressions of CD62p and PAC-1 on platelet surface were determined by FCM of trace whole blood after platelet activated by ADP in patients with new diagnosed AL (group I), complete remission (CR, group II) and continuously complete remission (CCR, group III). Healthy adults were used as control group. The result showed that the expression of CD62p in group I and II was higher than that in control group, before and after platelet activated by ADP (P < 0.01). The expression of PAC-1 in group I was higher than that in control group (P < 0.01), the expression of PAC-1 in group II was lower than that in control group (P > 0.01), There was no significant difference in expression of CD62p and PAC-1 between group III and control group (P > 0.01), and no significant difference was found between AL group with megakaryocyte malignant pathological changes and AL group without megakaryocyte malignant pathological changes before platelet activated by ADP (P > 0.01). After platelet activated by ADP, the expression of PAC-1 in the former was lower than that in the latter (P < 0.01). It is concluded that (1) high level activated platelet in peripheral blood of AL patients show that interaction between activated platelet and leukemia cells can be one of reason resulting in widespread hemorrhage and infiltration AL patiens; (2) the decrease of number and activted function of platelet at the first stage of AL patients may be caused by malignant hyperplasia of leukemia cells and damage of megakaryopoiesis in bone marrow.

Acute Disease↗

PubMed2005

[The study of maxillary protraction face mask combined with orthodontics for complete unilateral cleft lip and palate patients].

PURPOSE: The purpose of this study was to evaluate the influence of maxillary protraction face mask combined with orthodontics on complete unilateral cleft lip and palate patients' jaws. METHODS: 14 patients with complete unilateral cleft of lip and palate were included. Lateral cephalometric films were taken before orthodontic treatment ,before protracting and after orthodontic treatment. The statistical data were compared and analysed by SPSS10.0. Student's t test was used to determine the effect of maxillary protraction face mask combined with orthodontic treatment on jaw growth before and after treatment. RESULTS: The treatment resulted in good outcomes: incisor's overjet of 2mm, stable occlusion and straight profile. The SNA angle had a significant increase (P<0.001). The SNB angle and mandibular plane angle (SN-MP) have no change (P>0.05). The convexity of angle had significant change (P<0.001). CONCLUSION: Orthopedic force combined orthodontic treatment on patients with UCLP can promote the development of maxilla, without significant effect on the mandible. The overjet and overbite were improved by increasing the clination of upper anterior teeth, compensating lingually on lower anterior teeth and moving the upper anterior forward. The profile was improved from concave to straight, maxillary protrusion was increased, upper lip was plumpand, and the relationship between upper and lower jaws was more compatible.

Cephalometry↗

PubMed2005

[Study on human leukocyte antigen G1 reducing xeno-cell-rejection by transfecting porcine endothelial cells].

OBJECTIVE: To study whether the porcine endothelial cells (PECs) lines transfected by HLA-G1 can alter the lysis mediated by human peripheral blood mononuclear cell (PBMC) and natural killer cell 92 (NK-92). METHODS: By use of liposomes pack, the pcDNA3. 0 eukaryotic expression vector carrying HLA-G1 was transfected into PECs. Using indirect immunofluorescence and RT-PCR assays, the HLA-G1 expression in PECs was detected. The alteration of the lysis mediated by PBMC and NK-92 was detected by 51Cr-release assays. RESULTS: HLA-G1 expression could be detected in PECs after transfection of HLA-G1 at the levels of protein and RNA. It also could be found that the survival rate of transfected PECs was much higher than that of non-transfected PECs, when both of them faced the lysis mediated by human PBMC and NK-92. After transfecting the expression of HLA-G1 could be found in the transfected PECs and the lysis mediated by PBMC and NK-92 to PECs decreased obviously (P<0.05). CONCLUSION: The PECs transfected by HLA-G1 can decrease the NK lysis, so that it may provide us a new thought to inhibit the xeno-cell-rejection.

Animals↗

PubMed2005

[Effect on development in NT embryos after transplantation of nuclei derived from transfected goat fetal fibroblasts suffering different treatments into enucleate eggs].

In order to improve the development rate of preimplantation nuclear transfer embryos (NT embryos) after transplanting nuclei derived from transgenic goat fetal cells, the donor fetal fibroblasts starved for 5 days in DMEM containing 0.5% FCS were divided into three groups and treated with different methods respectively before using as donor cell. Group 1 was frozen at -80 degrees C or in liquid nitrogen for several days or months. Group 2 was at first treated as the same as group 1, then cultured for 2-5 days in DMEM containing 10% FCS and starved for another 5 days subsequently. Group 3 was cultured for 2-5 days in DMEM containing 10% FCS and starved for another 5 days subsequently. The rate of G0/G1 phase cells from group 2 was 95.68% and significantly different from group 1's 88.66%. The rate of survival cells from group 2 was 99.9% and significantly different from group 1's 80.00% (P < 0.05).The morula- blastocyst stage NT embryos development rate of group 2 was 66.09% and significantly different from group 1's 22.00% and group 3's 50.51% (P < 0.05). All NT embryos of above three groups were transferred into synchronous oestrus recipients and the pregnant status of recipients was checked by B-mode ultrasound diagnosis after 35 days. The recipient pregnancy rate of group 2 was 45.83%, much higher than that of group 1(20.00%) and group 3 (29.58%). The result of this experiment showed that donor cells treated with freezing and two times starvation could significantly improve the rate of G0/G1 phase cells, the rate of survival cells, the NT embryos development rate and the recipient pregnancy rate.

Animals↗

PubMed2005

[Isolation and functional identification of delta 5 desaturase gene from Mortierella alpina].

Arachidonic acid is an essential fatty acid in human nutrition and a biogenetic precursor of the biologically active prostaglandins and leukotrienes. delta5 desaturase is a key enzyme in the biosynthetic pathway of arachidonic acid, which catalyze the delta5 dehydrogenation of di-homo-gamma-linolenic acid to form arachidonic acid. Complete cDNA encoding putative delta5 fatty acyl desaturase was isolated from Mortierella alpina M6 via RT-PCR. The full length cDNA consisted of 1366 nucleotides encoding 446 amino acids. The deduced protein had conserved domains of known delta5 fatty acyl desaturases including a cytochrome b5 domain in the N terminal and 3 conserved histidine box. To elucidate the function of the protein, the cDNA was subcloned into the expression vector pPIC9K. The resultant recombinant plasmid pPIC9K-D5 was transformed to Pichia pastoris GS115 by electroporation. Transformants containing multi-copy delta5 desaturase gene were screened by Geneticin resistance. The transformants were induced to express the inserted gene with methanol when di-homo-gamma-linolenic acid was provided as an exogenous substrate. Analysis of the recombinant yeast lipids by gas chromatograph showed that a novel peak corresponding to the standard of arachidonic acid was detected. The novel peak was further characterized by GC-MS and identified as arachidonic acid. The results showed that the gene isolated from fungi Mortierella alpina M6 was a delta5 desaturase gene.

Amino Acid Sequence↗

PubMed2005

[The effect of sodium doecyl sulfate on Streptococcus sanguis biofilm].

PURPOSE: To investigate the effects of sodium doecyl sulfate on Streptococcus sanguis biofilm. METHODS: Streptococcus sanguis biofilm was formed on saliva-coated glass(SCG) in a flow culture system, then exposed to different dental plaque control agents for 3,10,30 minutes including A: 300 mmol.L(-1) sodium doecyl sulfate (SDS); B: 2% chlorhexidine combined with 300 mmol.L(-1) SDS; C: 0.3%triclosan combined with 300 mmol.L(-1) SDS. Confocal laser scanning microscopy and vital/dead fluorescent staining technique (vital stained green, dead stained red) were combined to observe biofilm thickness, bacterial density and viability, analysis of variance was used for comparison. RESULTS: The biofilm thickness and bacteria density reduced after treatment by 300 mmol.L(-1) SDS. However, there was no significant difference after treatment by 2% chlorhexidine combined with 300 mmol.L(-1)SDS; When treated by 0.3% triclosan combined with 300 mmol.L(-1) SDS, most or all of the bacteria detached from the surface and dispersed. CONCLUSIONS: The combination of SDS (aimed at detachment) and triclosan (aimed at killing bacteria) may be most effective in controlling biofilm.

Biofilms↗

PubMed2005

[Relationship of vascular endothelial growth factor-C and lymphangiogenesis with the development and prognosis of colon cancer].

OBJECTIVE: To study the correlation of vascular endothelial growth factor-C (VEGF- C) expression and lymphatic microvessel density (LMVD) with clinicopathological features and prognosis in colon cancer. METHODS: The expression of VEGF-C and VEGFR-3 was detected by immunohistochemical staining with monoclonal antibodies against VEGF-C and VEGFR-3 in 44 cases with primary colon cancer. LMVD was calculated. RESULTS: VEGF-C positive rate was 43.2% (19/44). VEGF-C expression was associated with tumor (P=0.003), lymph node metastasis (P=0.002), Dukes stage (P=0.001). The mean LMVD was 10.14+/- 4.19. LMVD was associated with lymph node metastasis (P=0.002), Dukes stage (P=0.001). LMVD in VEGF-C(+) group was (11.34+/- 4.83) higher than (9.24+/- 3.48) in VEGF-C(-) group, but there was no statistically significance between the two groups (P=0.105). The survival rate of the patients with positive VEGF-C was lower than that with negative VEGF-C (P=0.0225). The median survival time of the patients with LMVD(+) group was shorter than that with LMVD(-) (P=0.0036). Distant metastasis (P=0.0004), lymphatic metastasis (P=0.021) and LMVD (P=0.0469) were independent prognostic factors. CONCLUSIONS: VEGF-C and LMVD appear to be new prognostic factors for colon cancer. Furthermore, LMVD may be a new independent prognostic factor.

Adult↗

PubMed2005

[Therapeutic effect of phacoemulsification for closed-angle glaucoma].

OBJECTIVE: To investigate the therapeutic effect of phacoemulsification for primary closed-angle glaucoma complicated with cataract. METHODS: Phacoemulsification with posterior chamber foldable intraocular lens implantation was performed in 55 cases (58 eyes) of acute or chronic primary closed-angle glaucoma complicated with cataract. The changes of visual acuity, intraocular pressure, central anterior chamber depth and anterior chamber angle were observed after operation and the patients were followed up for 6 months. RESULTS: Compared with those before operation, the postoperative best corrected visual acuity and anterior chamber depth were improved, the intraocular pressure was reduced, and the closed chamber angle was partially reopened. CONCLUSION: Phacoemulsification with posterior chamber foldable intraocular lens implantation not only improves the visual acuity but also controls the intraocular pressure, and can be a valuable method for treating primary closed-angle glaucoma with cataract.

Aged↗

PubMed2004

A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis.

The incidence of tuberculosis has been increasing substantially on a worldwide basis over the past decade, but no tuberculosis-specific drugs have been discovered in 40 years. We identified a diarylquinoline, R207910, that potently inhibits both drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro (minimum inhibitory concentration 0.06 mug/ml). In mice, R207910 exceeded the bactericidal activities of isoniazid and rifampin by at least 1 log unit. Substitution of drugs included in the World Health Organization's first-line tuberculosis treatment regimen (rifampin, isoniazid, and pyrazinamide) with R207910 accelerated bactericidal activity, leading to complete culture conversion after 2 months of treatment in some combinations. A single dose of R207910 inhibited mycobacterial growth for 1 week. Plasma levels associated with efficacy in mice were well tolerated in healthy human volunteers. Mutants selected in vitro suggest that the drug targets the proton pump of adenosine triphosphate (ATP) synthase.

Amino Acid Sequence↗

PubMed2004

The origin of the internal nostril of tetrapods.

The choana, a unique 'internal nostril' opening from the nasal sac into the roof of the mouth, is a key part of the tetrapod (land vertebrate) respiratory system. It was the first component of the tetrapod body plan to evolve, well before the origin of limbs, and is therefore crucial to our understanding of the beginning of the fish-tetrapod transition. However, there is no consensus on the origin of the choana despite decades of heated debate; some have claimed that it represents a palatally displaced external nostril, but others have argued that this is implausible because it implies breaking and rejoining the maxillary-premaxillary dental arcade and the maxillary branch of nerve V. The fossil record has not resolved the dispute, because the choana is fully developed in known tetrapod stem-group members. Here we present new material of Kenichthys, a 395-million-year-old fossil fish from China, that provides direct evidence for the origin of the choana and establishes its homology: it is indeed a displaced posterior external nostril that, during a brief transitional stage illustrated by Kenichthys, separated the maxilla from the premaxilla.

Animals↗

PubMed2004

[Application of hyperglycemic clamp technique in the assessment of beta-cell function in obese individuals with glucose intolerance].

OBJECTIVE: To study the changes of insulin secretion in Chinese individuals with impaired glucose tolerance and diabetes and the relationship between insulin release and overweight/obesity. METHODS: Sixty-four individuals were divided into 6 groups according to glucose tolerance (GT) and body weight: normal weight with normal glucose tolerance (NW-NGT) group, NW with impaired glucose tolerance (NW-IGT) group, NW with diabetes (NW-DM) group, overweight or obese (OW/OB) with NGT (OW/OB-NGT) group, OW/OB with IGT (OW/OB-IGT) group, OW/OB with DM (OW/OB-DM) group. The subjects were required to fast for 12 hours and then underwent oral glucose tolerance test (OGTT) and hyperglycemic clamp. RESULTS: 1. The first-phase insulin release, the sum of insulin concentrations during the first 10 minutes (at the 2(nd), 4(th), 6(th), 8(th), and 10(th) minutes) were 186 mU/L +/- 38 mU/L in the IGT groups, significantly lower than that of the NGT groups (P = 0.001). The first-phase insulin release of the DM groups was 71 mU/L +/- 10 mU/L, significantly lower than those of the NW-NGT group and IGT group (257 mU/L +/- 22 mU/L and 164 mU/L +/- 47 mU/L respectively, both P < 0.01). The second-phase insulin release, the average insulin concentration during the 20th to 150th minutes of the DM groups was 31 mU/L +/- 4 mU/L, significantly lower than those of the NGT and IGT groups (74 mU/L +/- 5 mU/L and 45 mU/L +/- 19 mU/L, P < 0.01 and P < 0.04). The 2nd-phase insulin release was not significantly different between the NGT and IGT groups (P = 0.13). The maximum insulin release (INS-Max), the average insulin concentration during the last 30 minutes (120th to 150th minutes), of the DM groups was 40 mU/L +/- 6 mU/L, significantly lower than those of the NGT and IGT groups (P < 0.05). The INS-MAX was not significantly different between the NGT and IGT groups (P = 0.12). The first-phase insulin release, second-phase insulin release, and INS-MAX of the NW-IGT group were 164 mU/L +/- 47 mU/L, 45 mU/L +/- 19 mU/L, and 53 mU/L +/- 22 mU/L respectively, all significantly higher than those of the NW-IGT group (61 mU/L +/- 17 mU/L, 27 mU/L +/- 5 mU/L, and 34 mU/L +/- 6 mU/L respectively, P < 0.05) and those of the DM groups (61 mU/L +/- 17 mU/L, 27 mU/L +/- 5 mU/L, and 34 mU/L +/- 6 mU/L respectively, P < 0.05). 3. The first-phase insulin release, second-phase insulin release, and INS-MAX of the OW/OB-NGT group were 546 mU/L +/- 62 mU/L, 138 mU/L +/- 18 mU/L, and 163 mU/L +/- 24 mU/L respectively, all significantly higher than those of the NW-NGT group (257 mU/L +/- 22 mU/L, 74 mU/L +/- 6 mU/L, and 97 mU/L +/- 8 mU/L, respectively, P < 0.05). The first- phase insulin secretion in the OW/OB-IGT group and OW/OB-DM group were 201 mU/L +/- 47 mU/L and 82 mU/L +/- 9 mU/L respectively, both significantly lower than that of the OW/OB- NGT group (P < 0.05). CONCLUSION: 1. The insulin release is progressively decreased in Chinese individuals with IGT and DM. The individuals with IGT have lower first phase insulin release. In addition to decreased first phase insulin release, subjects with DM have reduced second-phase and maximum insulin release. 2. Simply overweight/obese individuals have higher insulin secretion, while overweight or obese individuals with IGT and DM have reduced first phase insulin release.

Adult↗

PubMed2004

[Regulation of G protein-coupled receptor kinase 5 mRNA and protein level in rat brain by addictive drugs].

G protein-coupled receptor kinase 5 (GRK5) plays an important role in the regulation of GPCR-transduced signals. Our previous study showed that acute administration of morphine could significantly increase GRK5 mRNA level in the cerebral cortex and hippocampus of the rat brain. The current study investigated the potential effects of acute administration of addictive drugs including morphine, heroine and cocaine on GRK5 mRNA level in the rat brain using in situ hybridization and analyzed the effects of acute and chronic morphine treatments on GRK5 protein level in the rat brain using Western blotting assay. Our results showed that 2 h after the initial morphine (10 mg/kg), cocaine (15 mg/kg) and heroine (1 mg/kg) treatment, the mRNA level of GRK5 in the parietal cortex increased about 110% (P<0.01), 70% (P<0.05) and 100% (P<0.01), respectively. In the temporal cortex, GRK5 mRNA level increased about 90% (P<0.01), 40% (P<0.05) and 80.0% (P<0.01), respectively . In the hippocampus, the mRNA level of GRK5 increased about 60% (P<0.01), 30% (P<0.05) and 80% (P<0.01). However, the mRNA level of GRK5 remained unchanged after acute morphine, cocaine or heroine treatment. In the cerebral cortex of the rat brain, the acute administration of morphine (NS-Mor) increased GRK5 protein level by about 60% while the chronic morphine treatment (Mor-Mor) increased GRK5 protein level even higher [about 130% compared with the control group (chronic saline treatment, NS-NS) group, P<0.01]. In the hippocampus, GRK5 protein level remained unchanged after acute administration of morphine (P>0.1),while the level of GRK5 protein tended to decrease after chronic morphine treatment (P=0.098). In the thalamus, acute morphine treatment caused no change in GRK5 protein level (P>0.1) while after chronic morphine treatment, GRK5 protein level decreased significantly (more than 90%, P<0.01), Taken together, our results indicate that addictive drugs can regulate GRK5 in the rat brain on protein level as well as on mRNA level and suggest that GRK5 may play a role in addiction of psychoactive substances.

Animals↗

PubMed2004

Gap junctional communication is required to maintain mouse cortical neural progenitor cells in a proliferative state.

The mechanisms that determine whether neural stem cells remain in a proliferative state or differentiate into neurons or glia are largely unknown. Here we establish a pivotal role for gap junction-mediated intercellular communication in determining the proliferation and survival of mouse neural progenitor cells (NPCs). When cultured in the presence of basic fibroblast growth factor (bFGF), NPCs express the gap junction protein connexin 43 and are dye-coupled. Upon withdrawal of bFGF, levels of connexin 43 and dye coupling decrease, and the cells cease proliferating and differentiate into neurons; the induction of gap junctions by bFGF is mediated by p42/p44 mitogen-activated protein kinases. Inhibition of gap junctions abolishes the ability of bFGF to maintain NPCs in a proliferative state resulting in cell differentiation or cell death, while overexpression of connexin 43 promotes NPC self-renewal in the absence of bFGF. In addition to promoting their proliferation, gap junctions are required for the survival of NPCs. Gap junctional communication is therefore both necessary and sufficient to maintain NPCs in a self-renewing state.

Animals↗

PubMed2004

The flavonoid baicalein inhibits fibrillation of alpha-synuclein and disaggregates existing fibrils.

The aggregation of alpha-synuclein has been implicated as a critical step in the development of Parkinson's disease. Parkinson's disease is a progressive neurodegenerative disorder caused by the loss of dopaminergic neurons from the substantia nigra; currently, no cure exists. Baicalein is a flavonoid with antioxidant properties; upon oxidation, it forms several products including quinones. We show here that low micromolar concentrations of baicalein, and especially its oxidized forms, inhibit the formation of alpha-synuclein fibrils. In addition, existing fibrils of alpha-synuclein are disaggregated by baicalein. The product of the inhibition reaction is predominantly a soluble oligomer of alpha-synuclein, in which the protein molecules have been covalently modified by baicalein quinone to form a Schiff base with a lysine side chain in alpha-synuclein. The binding of baicalein was abolished by conversion of the Tyr residues into Phe, demonstrating that Tyr is involved in the interaction of alpha-synuclein with baicalein. In disaggregation baicalein causes fragmentation throughout the length of the fibril. These observations suggest that baicalein and similar compounds may have potential as therapeutic leads in combating Parkinson's disease and that diets rich in flavonoids may be effective in preventing the disorder.

Anaerobiosis↗

PubMed2004

Dopamine and L-dopa disaggregate amyloid fibrils: implications for Parkinson's and Alzheimer's disease.

Protein deposition diseases involve the aggregation of normally soluble proteins, leading to both fibrillar and amorphous deposits. The aggregation of alpha-synuclein is associated with Parkinson's disease, and the aggregation of the Abeta peptide is associated with Alzheimer's disease. Here we show that L-dopa, dopamine, and other catecholamines dissolve fibrils of alpha-synuclein and Abeta peptide generated in vitro. The catecholamines also inhibited the fibrillation of these proteins. In addition, intraneuronal alpha-synuclein deposits formed in a mouse model were dissolved by incubation of tissue slices with L-dopa. These catecholamines are susceptible to oxidative breakdown, and we show that oxidation products are more effective than the parent compounds in inhibition. The ability to dissolve fibrils provides a new approach for studying mechanisms and consequences (e.g., the relationship between fibril formation and neurodegeneration) of protein aggregation. It is also likely to help in the development of strategies for the prevention and treatment of protein deposition diseases.

Alzheimer Disease↗