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| 1 | Dihydromyricetin and Salvianolic acid B inhibit alpha-synuclein aggregation and enhance chaperone-mediated autophagy显示文摘Background:Progressive accumulation ofα-synuclein is a key step in the pathological development of Parkinson’s disease.Impaired protein degradation and increased levels ofα-synuclein may trigger a pathological aggregation in vitro and in vivo.The chaperone-mediated autophagy(CMA)pathway is involved in the intracellular degradation processes ofα-synuclein.Dysfunction of the CMA pathway impairsα-synuclein degradation and causes cytotoxicity.Results:In the present study,we investigated the effects on the CMA pathway andα-synuclein aggregation using bioactive ingredients(Dihydromyricetin(DHM)and Salvianolic acid B(Sal B))extracted from natural medicinal plants.In both cell-free and cellular models ofα-synuclein aggregation,after administration of DHM and Sal B,we observed significant inhibition ofα-synuclein accumulation and aggregation.Cells were co-transfected with a Cterminal modifiedα-synuclein(SynT)and synphilin-1,and then treated with DHM(10μM)and Sal B(50μM)16 hours after transfection;levels ofα-synuclein aggregation decreased significantly(68%for DHM and 75%for Sal B).Concomitantly,we detected increased levels of LAMP-1(a marker of lysosomal homeostasis)and LAMP-2A(a key marker of CMA).Immunofluorescence analyses showed increased colocalization between LAMP-1 and LAMP-2A withα-synuclein inclusions after treatment with DHM and Sal B.We also found increased levels of LAMP-1 and LAMP-2A both in vitro and in vivo,along with decreased levels ofα-synuclein.Moreover,DHM and Sal B treatments exhibited anti-inflammatory activities,preventing astroglia-and microglia-mediated neuroinflammation in BAC-α-syn-GFP transgenic mice.Conclusions:Our data indicate that DHM and Sal B are effective in modulatingα-synuclein accumulation and aggregate formation and augmenting activation of CMA,holding potential for the treatment of Parkinson’s disease. | Jia-Zhen Wu Mustafa Ardah Caroline Haikal Alexander Svanbergsson Meike Diepenbroek Nishant N.Vaikath Wen Li Zhan-You Wang Tiago F.Outeiro Omar M.El-Agnaf Jia-Yi Li | 2019 | Translational Neurodegeneration2019，8，1： | 11 |
| 2 | Age-Dependent Alpha-Synuclein Accumulation and Phosphorylation in the Enteric Nervous System in a Transgenic Mouse Model of Parkinson's Disease显示文摘The enteric nervous system(ENS) controls the function of the gastrointestinal tract and has been implicated in various diseases, including Parkinson's disease(PD). PD is a neurodegenerative disease with Lewy bodies(LBs) and Lewy neurites(LNs) as the main pathological features. In addition to the typical motor symptoms in PD,attention has been drawn to non-motor symptoms, such as constipation, implying dysfunction of the ENS. In the present study, we characterized the age-dependent morphological alterations and aggregation of a-synuclein(asyn), the primary protein component in LBs and LNs, in the ENS in an a-syn transgenic mouse model. We found that the expression and accumulation of a-syn increased gradually in neurons of Meissner's and Auerbach's plexuses of the gastrointestinal tract with age(from 1 week to 2 years). In addition, a-syn was increasingly phosphorylated at the serine 129 residue, reflecting pathological alterations of the protein over time. Furthermore, asyn was present in different subtypes of neurons expressing vasoactive intestinal polypeptide, neuronal nitric oxide synthase, or calretinin. The results indicated that BAC-aSyn-GFP transgenic mice provide a unique model in which to study the relationship between ENS and PD pathogenesis. | Chong-Bin Zhong Qian-Qian Chen Caroline Haikal Wen Li Alexander Svanbergssona Meike Diepenbroek Jia-Yi Li | 2017 | Neuroscience Bulletin2017，33，5： | 5 |
| 3 | NPC1L1 and SR-BI are involved in intestinal cholesterol absorption from small-size lipid donors 显示文摘 | Haikal Z Play B Landrier JF | 2008 | Lipids2008，43，5： | 1 |
| 4 | Advantages of the rapid HIV-1 Test in occupational accidents with potentially contaminated material among health workers显示文摘 | Alcyone Artioli MACHADO Roberto MARTINEZ Amira Aparecida HAIKAL | 2001 | Rev Inst Med trop Sao Paulo2001，43，4： | 1 |
| 5 | Cross-sectional geounetry of the sacral ala for safe insertion of iliosacral lag screws: A computed tomography model显示文摘 | Noojin FK Malkani AL Haikal L | 2000 | J Orthop Trauma2000，14，： | 1 |
| 6 | Cross-sectional geometry of the sacral ala for safe insertion of iliosacral lag screws: a computed tomography model显示文摘 | Noojin FK Malkani AL Haikal L | 2000 | J Orthop Trauma2000，14，1： | 1 |
| 7 | Adaptive neuro-fuzzy control of an induction motor显示文摘 | Fayez G. Areed Amira Y. Haikal Reham H. Mohammed | 2010 | Ain Shams Engineering Journal2010，，1： | 1 |
| 8 | Obesity is associated with insulin resistance and components of the metabolic syndrome in Lebanese adolescents显示文摘 | Lara Nasreddine Farah Naja Maya Tabet Mohammad-Zuheir Habbal Aida El-Aily Chrystel Haikal Samira Sidani Nada Adra Nahla Hwalla | 2012 | Annals of Human Biology2012，，2： | 1 |
| 9 | Cross-sectional geometry of the sacral ala for safe insertion of iiiosacral lagscrews : a computed tomography model 显示文摘 | Ncojin FK Malkani AL Haikal L etal | 2000 | J Orthop Trauma2000，14，1： | 1 |
| 10 | Cross-sectional geometry of the sacral ala for safe insertion of iliosacral lag screws : a com- puted tomography model 显示文摘 | Noojin FK Malkani AL Haikal L | 2000 | J Orthop Trauma2000，14，1： | 1 |
| 11 | Cross-sectionalgeometry of the sacral ala for safe insertion of iliosacral lagscrews: a computed tomography model 显示文摘 | Noojin FK Malkani AL Haikal L | 2000 | J Orthop Trauma2000，14，1： | 1 |
| 12 | Cross-sectional geometry of the sacral ala for safe insertion of iliosacral lag screws:a computed tomography model显示文摘 | Noojin FK Malkani AL Haikal L | | 0，，01： | 1 |
| 13 | Cross-sectional geometry of the sacral ala for safe insertion of iliosacral lag screws:a computed tomography model显示文摘 | Noojin FK Malkani AL Haikal L | 2000 | J Orthop Trauma2000，14，1： | 1 |
| 14 | Age-dependent alpha-synuclein accumulation and aggregation in the colon of a transgenic mouse model of Parkinson’s disease显示文摘Background:Parkinson’s disease(PD)is one of the most common neurodegenerative diseases,neuropathologically characterized by misfolded protein aggregation,called Lewy bodies and Lewy neurites.PD is a slow-progressive disease with colonic dysfunction appearing in the prodromal stage and lasting throughout the course of the disease.Methods:In order to study PD pathology in the colon,we examined the age-dependent morphological and pathological changes in the colon of a PD mouse model expressing human wildtype α-synuclein(α-syn)fused with the green fluorescent protein(GFP),under the endogenous mouse α-syn promoter.Results:We observed an age-dependent progressive expression and accumulation of α-syn-GFP in the enteric neurons of Meissner’s(submucosal)and Auerbach’s(myenteric)plexuses of the colon.Additionally,the phosphorylation of α-syn at serine 129 also increased with age and the aggregation ofα-syn-GFP coincided with the appearance of motor deficits at 9 months of age.Furthermore,α-syn(-GFP)distinctly co-localized with different subtypes of neurons,as identified by immunohistochemical labeling of vasoactive intestinal peptide(VIP),neuronal nitric oxide synthase(nNOS),and calretinin.Conclusions:Our results show the development of α-syn pathology in the enteric neurons of the colon in a PD mouse model,which coincide with the appearance of motor deficits.Our mouse model possesses the potential and uniqueness for studying PD gastrointestinal dysfunction. | Qian-Qian Chen Caroline Haikal Wen Li Ming-Tao Li Zhan-You Wang Jia-Yi Li | 2018 | Translational Neurodegeneration2018，7，1： | 1 |
| 15 | Hemodialysis catheter-associated fibrin sheaths:Treatment with a low-dose rt-PA infusion显示文摘 | Savader SJ Haikal LC Ehrman KO | 2000 | J Vasc Interv Radiol2000，11，： | 1 |
| 16 | Cross-sectional geometry of the sacral ala for safe insertion of iliosacral lag screws:a computed tomography model 显示文摘 | Noojin FK Malkani AL Haikal L | 2000 | J Orthop Trauma2000，14，1： | 1 |
| 17 | Hemodialysis catheter-associate fibrin sheaths: treatment with a low-dose rt- PA infusion显示文摘 | Savader SJ Haikal LC Ehrman KO | 2000 | J Vase Interv Radiol2000，11，9： | 1 |
| 18 | Cross -sectional geometry of the sacral ala for safe insertion of iliosacral lag screws: a computed tomography model显示文摘 | Malkani AL Haikal L | 2000 | J Orthop Trauma2000，14，： | 1 |
| 19 | Modified culturalbased genetic algorithm for optimization显示文摘 | Amira Haikal Mostafa El-Hosseni | 2011 | J of Ain Shams Engineering2011，2，34： | 1 |
| 20 | Differential seeding and propagating efficiency ofα-synuclein strains generated in different conditions显示文摘Background:Accumulation of alpha-synuclein(α-syn)is a main pathological hallmark of Parkinson’s and related diseases,which are collectively known as synucleinopathies.Growing evidence has supported that the same protein can induce remarkably distinct pathological progresses and disease phenotypes,suggesting the existence of strain difference amongα-syn fibrils.Previous studies have shown thatα-syn pathology can propagate from the peripheral nervous system(PNS)to the central nervous system(CNS)in a“prion-like”manner.However,the difference of the propagation potency from the periphery to CNS among differentα-syn strains remains unknown and the effect of different generation processes of these strains on the potency of seeding and propagation remains to be revealed in more detail.Methods:Three strains of preformedα-syn fibrils(PFFs)were generated in different buffer conditions which varied in pH and ionic concentrations.Theα-syn PFFs were intramuscularly(IM)injected into a novel bacterial artificial chromosome(BAC)transgenic mouse line that expresses wild-type humanα-syn,and the efficiency of seeding and propagation of these PFFs from the PNS to the CNS was evaluated.Results:The three strains ofα-syn PFFs triggered distinct propagation patterns.The fibrils generated in mildly acidic buffer led to the most severeα-syn pathology,degeneration of motor neurons and microgliosis in the spinal cord.Conclusions:The differentα-syn conformers generated in different conditions exhibited strain-specific pathology and propagation patterns from the periphery to the CNS,which further supports the view thatα-syn strains may be responsible for the heterogeneity of pathological features and disease progresses among synucleinopathies. | Di Liu Jian-Jun Guo Ji-Hui Su Alexander Svanbergsson Lin Yuan Caroline Haikal Wen Li Gunnar Gouras Jia-Yi Li | 2021 | Translational Neurodegeneration2021，10，2： | 0 |
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