scholarly journals New aspects in pathogenesis of konzo: neural cell damage directly caused by linamarin contained in cassava (Manihot esculenta Crantz)

2003 ◽  
Vol 90 (2) ◽  
pp. 467-472 ◽  
Author(s):  
V. G. Sreeja ◽  
N. Nagahara ◽  
Q. Li ◽  
M. Minami
Keyword(s):  
Cell Death ◽  
Manihot Esculenta ◽  
Glucose Transporter ◽  
Cytochalasin B ◽  
Cell Damage ◽  
Spastic Paraparesis ◽  
Control Group ◽  
Neural Cells ◽  
Manihot Esculenta Crantz ◽  
Group 3

Epidemic spastic paraparesis (konzo) found in tropical and subtropical countries is known to be caused by long-term intake of cassava (Manihot esculenta Crantz), which contains a cyanoglucoside linamarin (α-hydroxyisobutyronitrile-β-D-glucopyranoside). It has been reported that linamarin is enzymatically converted to cyanide by bacteria in the intestine, and this is absorbed into the blood and then damages neural cells. However, unmetabolized linamarin was found in the urine after oral administration of cassava; thus, we hypothesized that konzo could be caused by direct toxicity of the unmetabolized linamarin that was transferred to the brain and could be transported into neural cells via a glucose transporter. In the present study it was confirmed that linamarin directly damaged neural culture pheochromocytoma cell (PC) 12 cells; 0·10 mM-linamarin caused cell death at 13·31 (SD 2·07) %, which was significantly different from that of control group (3·18 (SD 0·92) %, P=0·0004). Additional 10 μM-cytochalasin B, an inhibitor of a glucose transporter, prevented cell death: the percentage of dead cells significantly decreased to 6·06 (SD 1·98), P=0·0088). Furthermore, glucose also prevented cell death. These present results strongly suggest that linamarin competes with cytochalasin B and glucose for binding to a glucose transporter and enters into cells via glucose transporter.

scholarly journals P0985EFFECTS OF SILVER NANOPARTICLES ON RENAL FUNCTION IN FAT-FED AND STREPTOZOTOCIN-TREATED RATS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Pardeep Kumar
Keyword(s):  
Oxidative Stress ◽  
Silver Nanoparticles ◽  
Renal Function ◽  
Heat Shock ◽  
Insulin Receptor ◽  
Glucose Transporter ◽  
Control Group ◽  
Standard Diet ◽  
Glucose Transporter 2 ◽  
Group 3

Abstract Background and Aims The present study investigated the effects of silver nanoparticles on serum parameters of renal function, on oxidative stress markers (malondialdehyde [MDA] and 8-isoprostane), and on expression level of insulin receptor, glucose transporter 2 (GLUT2), glucokinase genes and heat-shock proteins (HSPs) in rats. Method Male Wistar rats (n=64, 10 weeks old) were divided into four groups. Group 1 received a standard diet (12% of calories as fat). Group 2 received a standard diet, plus silver nanoparticles (SNPs); received a single daily oral dose of SNP of 100 mg/kg in suspension. Group 3 received a high-fat diet (40% of calories as fat) for 2 weeks, and was then injected with streptozotocin (STZ) on day 14 (STZ, 40 mg/kg intraperitoneally). Group 4 was treated in the same way as group 3 (HFD/STZ), but was supplemented with SNP 100mg /kg/body weight/day. Oxidative stress in the kidneys of diabetic rats was evidenced by an elevation in levels of MDA and 8-isoprostane. Protein concentrations of insulin receptor, GLUT2, glucokinase genes and heat-shock (HSP60 and HSP70) in renal tissue were determined by Western blot analyses. Results SNP supplementation lowered kidney concentrations of MDA, 8-isoprostane levels, serum urea-N, and creatinine, and reduced the severity of renal damage in the STZ-treated group (i.e., the diabetes-induced group). The expression of insulin receptor, GLUT-2, glucokinase genes and HSPs was lower in the STZ group that received SNP than in the group that did not. No significant effect of SNP supplementation was detected in regard to the overall measured parameters in the control group. Conclusion This study supported the efficacy of SNP in reducing renal risk factors and impairment because of diabetes and act as potent antidiabetic agent.

scholarly journals Effect of cryopreservation on the cellular integrity of equine embryos

Reproduction ◽  
2005 ◽  
Vol 129 (6) ◽  
pp. 789-798 ◽  
Author(s):  
T Tharasanit ◽  
B Colenbrander ◽  
T A E Stout
Keyword(s):  
Cell Death ◽  
Cell Viability ◽  
Cytochalasin B ◽  
Cell Damage ◽  
Uterine Cavity ◽  
Trypsin Treatment ◽  
Embryo Survival ◽  
Embryo Size ◽  
Cellular Integrity ◽  
Cytoskeleton Integrity

Horse embryos are rarely cryopreserved in practice because expanded blastocysts tolerate freezing poorly, and the embryo begins expanding very soon after entering the uterine cavity. This study examined the effects of freezing on cytoskeleton integrity, and investigated whether cell damage could be reduced using trypsin to thin the blastocyst capsule or cytochalasin-B (cyto-B) to stabilise the cytoskeleton. Sixty-nine embryos were recovered 7 days after ovulation and equilibrated in 10% glycerol, with or without pretreatment with 0.2% trypsin or 7.5 μg/ml cyto-B. Forty-two of the embryos were frozen; the rest were used to determine whether pre-freezing treatment alone caused cell damage. Subsequently, embryos were stained with 4′,6-diamidino-2-phenylindole dihydrochloride, to identify dead cells, and fluorescently labelled phalloidin, to assess cytoskeleton quality. Without freezing, none of the treatments affected cell viability. And although Cyto-B altered actin distribution, the cytoskeleton returned to normal during a 4-h culture. Following cryopreservation, the percentage of dead cells (11.1 ± 1.3%) did not differ between treatments (P > 0.05), but significantly fewer cells died in small (≤300 μm) than in large embryos when neither pretreatment was used (P > 0.05); the effect of embryo size was, however, not significant after pretreatment with trypsin or cyto-B, and trypsin improved the likelihood of an intact cytoskeleton post thaw. However, trypsin treatment also resulted in a ‘sticky’ capsule that complicated embryo handling, and cyto-B-induced actin-depolymerisation was not reversed during a 6-h post-thaw incubation. Thus, while trypsin pretreatment improved cytoskeleton preservation and both trypsin and cyto-B may reduce cell death during cryopreservation of large embryos, both treatments induced other changes likely to compromise embryo survival.

scholarly journals Potensi ekstrak daun singkong (Manihot esculenta Crantz.) terhadap profil leukosit darah tepi model tikus disfungsi ovarium dan periodontitisPotential of cassava leaves (Manihot esculenta Crantz.) extract on peripheral blood leukocyte profile in ovary dysfunction and periodontitis rat model

2021 ◽  
Vol 33 (1) ◽  
pp. 44
Author(s):  
Lutfi Meiga Sari ◽  
Zahara Meilawaty ◽  
Pudji Astuti ◽  
Amandia Dewi Permana Shita ◽  
Agustin Wulan Suci Dharmayanti ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Manihot Esculenta ◽  
Leaf Extract ◽  
Peripheral Blood Leukocyte ◽  
Control Group ◽  
Ovarian Dysfunction ◽  
Blood Leukocytes ◽  
Manihot Esculenta Crantz ◽  
Control Group Design ◽  
Anti Inflammatory

Pendahuluan: Disfungsi ovarium merupakan keadaan ovarium yang mengalami kegagalan dalam sekresi hormon seks steroid. Penurunan sekresi hormon terutama estrogen dapat memicu peningkatan sitokin proinflamasi seperti IL-1, IL-6 dan TNF-α yang berperan dalam resorpsi tulang dan reaksi inflamasi periodontal. Salah satu drug of choice dari periodontitis adalah metronidazole. Penggunaan metronidazole secara sistemik dapat mengakibatkan efek samping, sehingga diperlukan bahan alternatif yang memiliki efek terapi antiinflamasi. Salah satu tanaman yang memiliki efek antiinflamasi adalah daun Singkong. Tujuan penelitian adalah menganalisis potensi ekstrak daun Singkong sebagai antiinflamasi terhadap profil leukosit darah tepi model tikus disfungsi ovarium dan periodontitis. Metode: Jenis penelitian eksperimental laboratoris dengan post-test only control group design. Sampel penelitian sebanyak 18 ekor tikus betina yang dibagi menjadi dua kelompok besar yakni kelompok disfungsi ovarium dan kelompok kecil periodontitis. Pembuatan model tikus disfungsi ovarium dan tikus periodontitis dilakukan selama 28 hari. Setelah masing-masing kelompok dibagi menjadi 3 kelompok yang diberikan perlakuan aquades, metronidazole dan ekstrak daun Singkong selama 7 hari. Setiap tikus diambil darahnya melalui plexus infraorbitalis pada hari ke-1, hari ke-3 dan hari ke-7. Darah yang diambil selanjutnya dilakukan perhitungan jumlah sel leukosit darah tepi menggunakan kamar hitung dan perhitungan jenis dengan cara visual. Hasil: Hasil uji LSD menunjukkan bahwa terdapat perbedaan bermakna jumlah leukosit darah tepi antar hari pada kelompok tikus yang mengalami disfungsi ovarium (p≤0,05). Simpulan: Ekstrak daun Singkong (Manihot esculenta Crantz) dapat menurunkan profil leukosit perifer model tikus disfungsi ovarium dan periodontitis.Kata kunci: Disfungsi ovarium, periodontitis, profil leukosit perifer, ekstrak daun singkong. ABSTRACTIntroduction: Ovarian dysfunction is when the ovaries fail in the secretion of steroid sex hormones. Decreased secretion of hormones, especially estrogen, can trigger an increase in pro-inflammatory cytokines such as IL-1, IL-6 and TNF-α, which play a role in bone resorption and periodontal inflammatory reactions. One drug of choice for periodontitis is metronidazole. Systemic use of metronidazole can cause side effects, so an alternative material with a therapeutic anti-inflammatory effect is needed. One of the plants that have an anti-inflammatory effect is cassava leaves. The research objective was to analyse the potential of cassava leaf extract as an anti-inflammatory against the peripheral blood leukocyte profile in a mouse model of ovarian dysfunction and periodontitis. Methods: This was an experimental laboratory study with a post-test only control group design. The research sample consisted of 18 female rats divided into two large groups: the ovarian dysfunction group and the small periodontitis group. The making of mouse models of ovarian dysfunction and periodontitis rats was carried out for 28 days. After each group was divided into three groups treated with distilled water, metronidazole and cassava leaf extract for seven days. Blood was drawn from each mouse through the infraorbital plexus on day 1, day three, and 7. The blood that was taken was then performed to calculate the number of peripheral blood leukocytes using the counting room and the calculation of the type by visual means. Results: The results of the LSD test showed that there was a significant difference in the number of peripheral blood leukocytes between days in the group of rats with ovarian dysfunction (p≤0.05). Conclusion: Cassava leaf extract (Manihot esculenta Crantz) can reduce the profile of peripheral leukocytes in a mouse model of ovarian dysfunction and periodontitis.Keywords: Ovarian dysfunction, periodontitis, peripheral leukocytes profile, cassava leaf extract.

scholarly journals PENGARUH PEMBERIAN EKSTRAK KULIT BATANG JALOH (Salix tetrasperma Roxb) DAN SERBUK DAUN SINGKONG (Manihot esculenta Crantz) TERHADAP PERTAMBAHAN BOBOT BADAN AYAM BROILER (Effect of Willow (Salix tetrasperma Roxb) Bark Extract and Cassava (Manihot esculenta Crantz) Leaf Powder Supplementation on Weight Gain of Broiler Chickens)

2016 ◽  
Vol 10 (1) ◽  
pp. 51 ◽  
Author(s):  
Hanum Harfinda ◽  
Rinidar Rinidar ◽  
T. Armansyah ◽  
Sugito Sugito ◽  
Mustafa Sabri ◽  
...  
Keyword(s):  
Weight Gain ◽  
Manihot Esculenta ◽  
Broiler Chickens ◽  
Bark Extract ◽  
Control Group ◽  
Manihot Esculenta Crantz ◽  
Randomized Design ◽  
Commercial Feed ◽  
Leaf Powder ◽  
Willow Bark

This study’s purpose is to determine the effect of supplementation of willow bark extract (1000 mg/L) in drinking water and 15% cassava leaf powder in feed on broiler weight gain. This study was designed using completely randomized design (CRD) in which 20 broiler chickens were divided into four treatment groups with five broiler per each treatment. Control group (P0) was only given commercial feed, P1 (commercial feed + cassava leaf powder), P2 (commercial feed + willow bark extract), and P3 (commercial feed + cassava leaf powder and willow bark extract). Data were analyzed using analysis of variance and followed by Duncan test. The results showed that P2 significantly different (P<0.01) compare to P0 and P3, and different (P>0.05) from P1. Group P1 was different (P<0.05) from group P3, but P3 showed no significant different (P>0.05) to P0 on weight gain. whereas feed intake was similar among treatments, however food conversion was differ among treatments. In conclusion, combination of willow bark extract and cassava leaf powder could not increase broiler chickens weight gain.

scholarly journals Potensi ekstrak daun singkong (Manihot esculenta Crantz) terhadap ekspresi MMP-8 fibroblas gingiva pada model tikus dengan disfungsi ovarium dan periodontitisPotential of cassava (Manihot esculenta Crantz) leaf extract on the MMP-8 expression of gingival fibroblast in rats model with ovarian dysfunction and periodontitis

2020 ◽  
Vol 32 (2) ◽  
pp. 105
Author(s):  
Zahara Meilawaty ◽  
Amandia Dewi Permana Shita ◽  
Paramudibta Lungit Kuncaraningtyas ◽  
Agustin Wulan Suci Dharmayanti ◽  
Zahreni Hamzah
Keyword(s):  
Porphyromonas Gingivalis ◽  
Manihot Esculenta ◽  
Leaf Extract ◽  
Control Group ◽  
Gingival Fibroblast ◽  
Sprague Dawley ◽  
Ovarian Dysfunction ◽  
Manihot Esculenta Crantz ◽  
Control Group Design ◽  
Post Test

Pendahuluan: Disfungsi ovarium merupakan kondisi yang menimbulkan defisiensi hormon estrogen dan progesteron. Penurunan hormonal ini menyebabkan peningkatan produksi tumor necrosis factor (TNF) yang dapat memicu peningkatan produksi matriks metalloproteinase-8 (MMP-8). Periodontitis yang disebabkan oleh bakteri gram negatif akan memicu makrofag melepaskan TNF-α yang berkontribusi dalam pembentukan MMP-8. MMP-8 ini berperan dalam degradasi kolagen jaringan ikat gingiva. Meningkatnya MMP-8 dapat menyebabkan terjadinya periodontitis. Gejala periodontitis karena disfungsi ovarium dan induksi bakteri ini dapat diperlambat dengan bahan alam, yaitu daun singkong. Tujuan penelitian ini adalah untuk menganalisis potensi ekstrak daun singkong (Manihot esculenta Crantz) terhadap ekspresi MMP-8 fibroblas pada model tikus disfungsi ovarium dan periodontitis. Metode: Penelitian ini merupakan penelitian eksperimental laboratoris dengan post-test only control group design. Sampel yang digunakan adalah tikus Sprague-Dawley betina yang dibagi dalam 5 kelompok yaitu (1) kelompok kontrol (K), (2) Kelompok yang diinduksi bakteri Porphyromonas gingivalis dan diberi aquades, (3) Kelompok yang diinduksi bakteri Porphyromonas gingivalis dan diberi ekstrak daun singkong, (4) Kelompok yang diberi perlakuan ovariektomi dan diberi aquades, (5) Kelompok yang dilakukan ovariektomi dan diberi ekstrak daun singkong. Pengambilan jaringan gingiva setelah tahap euthanasia dilakukan untuk pembuatan preparat histopatologi dengan pewarnaan imunohistokimia. Pengamatan dan penghitungan ekspresi MMP-8 dilakukan dengan menggunakan software ImageJ dan Immunoratio. Hasil: Hasil analisis data one-way ANOVA, ekspresi MMP-8 fibroblas gingiva menunjukkan perbedaan yang signifikan (p=0,000). Hal ini menunjukkan bahwa ekstrak daun singkong dapat menurunkan ekspresi MMP-8 fibroblas gingiva tikus yang mengalami disfungsi ovarium dan periodontitis diinduksi P. gingivalis. Simpulan: Ekstrak daun singkong (Manihot esculenta Crantz) dapat menurunkan ekspresi MMP-8 sel fibroblas gingiva pada model tikus disfungsi ovarium dan periodontitis.Kata kunci: Disfungsi ovarium, periodontitis, ekspresi MMP-8, ekstrak daun singkong. ABSTRACTIntroduction: Ovarian dysfunction is a condition that causes estrogen and progesterone deficiency. This hormonal decrease causes an increase in the production of Tumour Necrosis Factor (TNF), which can trigger an increase in the production of matrix metalloproteinase-8 (MMP-8). Periodontitis caused by gram-negative bacteria will trigger macrophages to release TNF-α, which contributes to the formation of MMP-8. MMP-8 plays a role in collagen degradation of the gingival connective tissue. An increase in MMP-8 can cause periodontitis. Periodontitis symptoms due to ovarian dysfunction and bacterial induction can be slowed down by natural ingredients, such as cassava leaf. The purpose of this study was to analyse the potential of cassava leaf extract (Manihot esculenta Crantz) on MMP-8 expression of gingival fibroblast in rats model with ovarian dysfunction and periodontitis. Methods: This study was an experimental laboratory with post-test only control group design. The samples were female Sprague-Dawley rats divided into five groups: (1) control group (K); (2) Porphyromonas gingivalis induced group and given aquadest; (3) Porphyromonas gingivalis induced and given cassava leaf extract; (4) Group with ovariectomy treatment and given aquadest; (5) Group with ovariectomy treatment and given cassava leaf extract. Gingival tissue retrieval after the euthanasia was carried out for the histopathology preparations by immunohistochemical staining. Observation and calculation of MMP-8 expressions were performed using ImageJ and Immunoratio software. Results: The results of the one-way ANOVA analysis of MMP-8 expression of gingival fibroblasts showed a significant difference (p = 0.000); thus cassava leaf extract reduce the MMP-8 expression of gingival fibroblasts of rats with ovarian dysfunction and P. gingivalis induced periodontitis. Conclusion: Cassava (Manihot esculenta Crantz) leaf extract can reduce the MMP-8 expression of gingival fibroblast cells in rats’ model with ovarian dysfunction and periodontitis.Keywords: Ovarian dysfunction, periodontitis, MMP-8 expression, cassava leaf extract.

scholarly journals Endosomal dysfunction in iPSC-derived neural cells from Parkinson’s disease patients with VPS35 D620N

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Keiko Bono ◽  
Chikako Hara-Miyauchi ◽  
Shunsuke Sumi ◽  
Hisayoshi Oka ◽  
Yasuyuki Iguchi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Apoptotic Cell ◽  
Induced Pluripotent Stem Cell ◽  
Control Group ◽  
Neural Cells ◽  
Endosomal Trafficking ◽  
Induced Pluripotent ◽  
Vacuolar Protein

Abstract Mutations in the Vacuolar protein sorting 35 (VPS35) gene have been linked to familial Parkinson’s disease (PD), PARK17. VPS35 is a key component of the retromer complex, which plays a central role in endosomal trafficking. However, whether and how VPS35 deficiency or mutation contributes to PD pathogenesis remain unclear. Here, we analyzed human induced pluripotent stem cell (iPSC)-derived neurons from PD patients with the VPS35 D620N mutation and addressed relevant disease mechanisms. In the disease group, dopaminergic (DA) neurons underwent extensive apoptotic cell death. The movement of Rab5a- or Rab7a-positive endosomes was slower, and the endosome fission and fusion frequencies were lower in the PD group than in the healthy control group. Interestingly, vesicles positive for cation-independent mannose 6-phosphate receptor transported by retromers were abnormally localized in glial cells derived from patient iPSCs. Furthermore, we found α-synuclein accumulation in TH positive DA neurons. Our results demonstrate the induction of cell death, endosomal dysfunction and α -synuclein accumulation in neural cells of the PD group. PARK17 patient-derived iPSCs provide an excellent experimental tool for understanding the pathophysiology underlying PD.

scholarly journals Comparison of the effects of cassava (Manihot esculenta Crantz) organic cyanide and inorganic cyanide on muscle and bone development in a Nigerian breed of dog

1992 ◽  
Vol 68 (2) ◽  
pp. 483-491 ◽  
Author(s):  
C. Ibebunjo ◽  
Beryl P. Kamalu ◽  
E. C. Ihemelandu
Keyword(s):  
Adverse Effect ◽  
Manihot Esculenta ◽  
Muscle Development ◽  
Bone Development ◽  
Muscle Protein ◽  
Sodium Cyanide ◽  
The Other ◽  
Control Group ◽  
Manihot Esculenta Crantz

Effects of cassava (Manihot esculenta Crantz)-borne organic cyanide and inorganic cyanide in the form of sodium cyanide on bone and muscle development were investigated in eighteen dogs of Nigerian breed. After 16 weeks of stabilization in the laboratory from the time of purchase when the dogs were fed on the same diet, they were randomly assigned to three experimental groups of six dogs each. The control group was fed on rice while the other two groups were fed on either cassava (gari) or rice plus cyanide. The three diets were made isoenergetic and isonitrogenous by varying the quantity of meat incorporated into them. The results obtained after 14 weeks of feeding the respective diets indicated that there was retardation of muscle development in the gari-fed dogs. This may have resulted from gluconeogenesis from muscle protein associated with suppression of production of insulin by the pancreas in this group. The results indicated also that the effects of inorganic dietary cyanides on muscle development were different. Both forms of dietary cyanides, however, had no adverse effect on bone development

scholarly journals Type 3 Resistant Starch Effect of Cassava (Manihot esculenta Crantz) on Fasting Blood Glucose in Diabetes Mellitus Wistar Rat Models

2018 ◽  
Vol 4 (3) ◽  
pp. 133
Author(s):  
T Ariani Widiastini ◽  
Elly Nurus Sakinah ◽  
Yudha Nurdian ◽  
Jauhar Firdaus
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Resistant Starch ◽  
Manihot Esculenta ◽  
Fasting Blood Glucose ◽  
Cassava Starch ◽  
Control Group ◽  
Manihot Esculenta Crantz ◽  
Rat Models ◽  
Type 3

Type 2 Diabetes Mellitus (T2DM) is a condition in which both insulin secretion and insulin sentivity disturbed. One of therapeutic approach of T2DM is through diet modification using resistant starch (RS) that has proven controlling both postprandial and fasting blood glucose. Cassava starch has 28,57% amylose and 51,24% amylopectin that can be increased through autoclaving-cooling process. Therefore, it can resist the digestion proess by amylose enzyme. The aim was to describe the effect of type 3 resistant starch cassava (Manihot esculenta Crantz) on fasting blood glucose (FBG) in Wistar diabetic rat models. This study was quasy experimental post-test only control group design using 16 Wistar rats divided into 4 groups, KN (normal), K- (DM), P1 (DM + cassava starch diet), and P2 (DM + type 3 RS cassava diet). High fat diet (HFD) and low dose streptozotocin (STZ) used as diabetic agents. Rats fed cassava starch or type 3 RS cassava diet for 28 days. GOD-PAP method used to measure the FBG level. The data analyzed using One Way ANOVA test with p>0,05 as significant value. The result shows no significant differences within experimental groups. Keywords: cassava, autoclaving-cooling, resistant starch, FBG

scholarly journals Endosomal Dysfunction in iPSC-Derived Neural Cells from Parkinson’s Disease Patients with VPS35 D620N

2020 ◽  
Author(s):  
Keiko Bono ◽  
Chikako Miyauchi-Hara ◽  
Shunsuke Sumi ◽  
Hisayoshi Oka ◽  
Yasuyuki Iguchi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Apoptotic Cell ◽  
Induced Pluripotent Stem Cell ◽  
Control Group ◽  
Neural Cells ◽  
Endosomal Trafficking ◽  
Induced Pluripotent ◽  
Vacuolar Protein

Abstract Mutations in the Vacuolar protein sorting 35 (VPS35) gene have been linked to familial Parkinson’s disease (PD), PARK17. VPS35 is a key component of the retromer complex, which plays a central role in endosomal trafficking. However, whether and how VPS35 deficiency or mutation contributes to PD pathogenesis remain unclear. Here, we analyzed human induced pluripotent stem cell (iPSC)-derived neurons from PD patients with the VPS35 D620N mutation and addressed relevant disease mechanisms. In the disease group, dopaminergic (DA) neurons underwent extensive apoptotic cell death. The movement of Rab5a- or Rab7a-positive endosomes was slower, and the endosome fission and fusion frequencies were lower in the PD group than in the healthy control group. Interestingly, vesicles positive for cation-independent mannose 6-phosphate receptor transported by retromers were abnormally localized in glial cells derived from patient iPSCs. Furthermore, we found a-synuclein accumulation in TH positive DA neurons. Our results demonstrate the induction of cell death, endosomal dysfunction and a-synuclein accumulation in neural cells of the PD group. PARK17 patient-derived iPSCs provide an excellent experimental tool for understanding the pathophysiology underlying PD.

Sign in / Sign up

Export Citation Format

Share Document