| GBA1 inactivation in oligodendrocytes affects myelination and induces neurodegenerative hallmarks and lipid dyshomeostasis in mice. | GBA1 inactivation in oligodendrocytes affects myelination and induces neurodegenerative hallmarks and lipid dyshomeostasis in mice.
Gregorio I, Russo L, Torretta E, Barbacini P, Contarini G, Pacinelli G, Bizzotto D, Moriggi M, Braghetta P, Papaleo F, Gelfi C, Moro E, Cescon M., Free PMC Article | 03/13/2024 |
| Whole Transcriptome Analysis of Substantia Nigra in Mice with MPTP-Induced Parkinsonism Bearing Defective Glucocerebrosidase Activity. | Whole Transcriptome Analysis of Substantia Nigra in Mice with MPTP-Induced Parkinsonism Bearing Defective Glucocerebrosidase Activity.
Usenko T, Bezrukova A, Rudenok MM, Basharova K, Shadrina MI, Slominsky PA, Zakharova E, Pchelina S., Free PMC Article | 08/19/2023 |
| The GBA1 D409V mutation exacerbates synuclein pathology to differing extents in two alpha-synuclein models. | The GBA1 D409V mutation exacerbates synuclein pathology to differing extents in two alpha-synuclein models.
Polinski NK, Martinez TN, Ramboz S, Sasner M, Herberth M, Switzer R, Ahmad SO, Pelligrino LJ, Clark SW, Marcus JN, Smith SM, Dave KD, Frasier MA., Free PMC Article | 06/11/2022 |
| Heterozygous GBA D409V and ATP13a2 mutations do not exacerbate pathological alpha-synuclein spread in the prodromal preformed fibrils model in young mice. | Heterozygous GBA D409V and ATP13a2 mutations do not exacerbate pathological α-synuclein spread in the prodromal preformed fibrils model in young mice.
Johnson ME, Bergkvist L, Stetzik L, Steiner JA, Meyerdirk L, Schulz E, Wolfrum E, Luk KC, Wesson DW, Krainc D, Brundin P. | 03/5/2022 |
| Wild-type GBA1 increases the alpha-synuclein tetramer-monomer ratio, reduces lipid-rich aggregates, and attenuates motor and cognitive deficits in mice. | Wild-type GBA1 increases the α-synuclein tetramer-monomer ratio, reduces lipid-rich aggregates, and attenuates motor and cognitive deficits in mice.
Glajch KE, Moors TE, Chen Y, Bechade PA, Nam AY, Rajsombath MM, McCaffery TD, Dettmer U, Weihofen A, Hirst WD, Selkoe DJ, Nuber S., Free PMC Article | 12/11/2021 |
| Decreased glucocerebrosidase activity and substrate accumulation of glycosphingolipids in a novel GBA1 D409V knock-in mouse model. | Decreased glucocerebrosidase activity and substrate accumulation of glycosphingolipids in a novel GBA1 D409V knock-in mouse model.
Polinski NK, Martinez TN, Gorodinsky A, Gareus R, Sasner M, Herberth M, Switzer R, Ahmad SO, Cosden M, Kandebo M, Drolet RE, Buckett PD, Shan W, Chen Y, Pellegrino LJ, Ellsworth GD, Dungan LB, Hirst WD, Clark SW, Dave KD., Free PMC Article | 10/30/2021 |
| Ocular phenotypes in a mouse model of impaired glucocerebrosidase activity. | Ocular phenotypes in a mouse model of impaired glucocerebrosidase activity.
Weber M, Min SW, Truong T, Hung J, Dale S, Reichelt M, Ubhayakar S, Cain-Hom C, Baca M, Jiang Z, Li Q, Brendza R, Lin H, Kung C, Forrest WF, Quiason-Huynh C, Sandoval W, Chen B, Deng Y, Easton A, Foreman O, Sene A, Bingol B., Free PMC Article | 10/16/2021 |
| Glucocerebrosidase deficiency promotes release of alpha-synuclein fibrils from cultured neurons. | Glucocerebrosidase deficiency promotes release of α-synuclein fibrils from cultured neurons.
Gegg ME, Verona G, Schapira AHV., Free PMC Article | 08/14/2021 |
| Behavioral Phenotyping in a Murine Model of GBA1-Associated Parkinson Disease. | Behavioral Phenotyping in a Murine Model of GBA1-Associated Parkinson Disease.
Do J, Perez G, Berhe B, Tayebi N, Sidransky E., Free PMC Article | 07/31/2021 |
| Impaired cellular bioenergetics caused by GBA1 depletion sensitizes neurons to calcium overload. | Impaired cellular bioenergetics caused by GBA1 depletion sensitizes neurons to calcium overload.
Plotegher N, Perocheau D, Ferrazza R, Massaro G, Bhosale G, Zambon F, Rahim AA, Guella G, Waddington SN, Szabadkai G, Duchen MR., Free PMC Article | 07/3/2021 |
| Glucocerebrosidase Gene Therapy Induces Alpha-Synuclein Clearance and Neuroprotection of Midbrain Dopaminergic Neurons in Mice and Macaques. | Glucocerebrosidase Gene Therapy Induces Alpha-Synuclein Clearance and Neuroprotection of Midbrain Dopaminergic Neurons in Mice and Macaques.
Sucunza D, Rico AJ, Roda E, Collantes M, González-Aseguinolaza G, Rodríguez-Pérez AI, Peñuelas I, Vázquez A, Labandeira-García JL, Broccoli V, Lanciego JL., Free PMC Article | 07/3/2021 |
| Lysosome and Inflammatory Defects in GBA1-Mutant Astrocytes Are Normalized by LRRK2 Inhibition. | Lysosome and Inflammatory Defects in GBA1-Mutant Astrocytes Are Normalized by LRRK2 Inhibition.
Sanyal A, DeAndrade MP, Novis HS, Lin S, Chang J, Lengacher N, Tomlinson JJ, Tansey MG, LaVoie MJ., Free PMC Article | 05/8/2021 |
| Systemic enzyme delivery by blood-brain barrier-penetrating SapC-DOPS nanovesicles for treatment of neuronopathic Gaucher disease. | Systemic enzyme delivery by blood-brain barrier-penetrating SapC-DOPS nanovesicles for treatment of neuronopathic Gaucher disease.
Sun Y, Liou B, Chu Z, Fannin V, Blackwood R, Peng Y, Grabowski GA, Davis HW, Qi X., Free PMC Article | 04/3/2021 |
| Reduced GCase activity does not result in aggregation of alpha-synuclein. However, in the context of extant misfolded alpha-synuclein, GCase activity modulates neuronal susceptibility to pathology. Furthermore, this modulation does not depend on neuron type but rather is driven by the level of pathological alpha-synuclein seeds. | Glucocerebrosidase Activity Modulates Neuronal Susceptibility to Pathological α-Synuclein Insult.
Henderson MX, Sedor S, McGeary I, Cornblath EJ, Peng C, Riddle DM, Li HL, Zhang B, Brown HJ, Olufemi MF, Bassett DS, Trojanowski JQ, Lee VMY., Free PMC Article | 07/11/2020 |
| Cognitive impairment was measured by two independent behavioural tests in heterozygous GBA1 mutant mice (D409V/WT). Reduced GBA1 GCase enzyme activity dis-equilibrates the finely balanced glycosphingolipid metabolism pathway. | Age-related neurochemical and behavioural changes in D409V/WT GBA1 mouse: Relevance to lewy body dementia.
Clarke E, Jantrachotechatchawan C, Buhidma Y, Broadstock M, Yu L, Howlett D, Aarsland D, Ballard C, Francis PT. | 05/16/2020 |
| In Gba(L444P/WT) knockin mice, the L444P heterozygous Gba mutation triggers mitochondrial dysfunction by inhibiting autophagy and mitochondrial priming, two steps critical for the selective removal of dysfunctional mitochondria by autophagy, a process known as mitophagy. | Mitochondrial dysfunction and mitophagy defect triggered by heterozygous GBA mutations.
Li H, Ham A, Ma TC, Kuo SH, Kanter E, Kim D, Ko HS, Quan Y, Sardi SP, Li A, Arancio O, Kang UJ, Sulzer D, Tang G., Free PMC Article | 03/14/2020 |
| Delivery of Glucosylceramidase Beta Gene Using AAV9 Vector Therapy as a Treatment Strategy in Mouse Models of Gaucher Disease. | Delivery of Glucosylceramidase Beta Gene Using AAV9 Vector Therapy as a Treatment Strategy in Mouse Models of Gaucher Disease.
Du S, Ou H, Cui R, Jiang N, Zhang M, Li X, Ma J, Zhang J, Ma D. | 03/14/2020 |
| Although the exact function of PGRN is unknown, it has been increasingly implicated in lysosomal physiology. Here we report that PGRN interacts with the lysosomal enzyme, glucocerebrosidase (GCase), and is essential for proper GCase activity. GCase activity is significantly reduced in tissue lysates from PGRN-deficient mice. | Progranulin deficiency leads to reduced glucocerebrosidase activity.
Zhou X, Paushter DH, Pagan MD, Kim D, Nunez Santos M, Lieberman RL, Overkleeft HS, Sun Y, Smolka MB, Hu F., Free PMC Article | 02/22/2020 |
| to create mouse model for PD, we crossed asyn Bacterial Artificial Chromosome transgenic mice with gba heterozygous knockout mice. These double-mutant (dm) mice express human asyn in a physiological manner through its native promoter and showed an increase in phosphorylated asyn in the regions vulnerable to PD, such as the olfactory bulb and dorsal motor nucleus of the vagus nerve | GBA haploinsufficiency accelerates alpha-synuclein pathology with altered lipid metabolism in a prodromal model of Parkinson's disease.
Ikuno M, Yamakado H, Akiyama H, Parajuli LK, Taguchi K, Hara J, Uemura N, Hatanaka Y, Higaki K, Ohno K, Tanaka M, Koike M, Hirabayashi Y, Takahashi R. | 02/8/2020 |
| The results of this study indicated that GBA1 deficiency due to D409H GBA1 mutation that contributes to alpha-synuclein accumulation exacerbates neuronal vulnerability in neurodegenerative processes triggered by A53T alpha-synuclein expression in vivo | D409H GBA1 mutation accelerates the progression of pathology in A53T α-synuclein transgenic mouse model.
Kim D, Hwang H, Choi S, Kwon SH, Lee S, Park JH, Kim S, Ko HS., Free PMC Article | 06/1/2019 |
| these results provide for the first time evidence that a decrease of GCase or overexpression of mutant GCase in a chronic in vivo setting can affect ASYN secretion. Such effects may mediate enhanced propagation of ASYN, driving pathology in GBA-associated Parkinson's disease | Modulation of β-glucocerebrosidase increases α-synuclein secretion and exosome release in mouse models of Parkinson's disease.
Papadopoulos VE, Nikolopoulou G, Antoniadou I, Karachaliou A, Arianoglou G, Emmanouilidou E, Sardi SP, Stefanis L, Vekrellis K. | 02/16/2019 |
| Thus, while the underlying mechanism is not clear, this model shows that gba deficiency impacts the age of onset and disease duration in aged SNCA(A53T) mice, providing a valuable resource to identify modifiers, pathways and possible moonlighting roles of glucocerebrosidase in Parkinson pathogenesis. | Glucocerebrosidase haploinsufficiency in A53T α-synuclein mice impacts disease onset and course.
Tayebi N, Parisiadou L, Berhe B, Gonzalez AN, Serra-Vinardell J, Tamargo RJ, Maniwang E, Sorrentino Z, Fujiwara H, Grey RJ, Hassan S, Blech-Hermoni YN, Chen C, McGlinchey R, Makariou-Pikis C, Brooks M, Ginns EI, Ory DS, Giasson BI, Sidransky E., Free PMC Article | 09/1/2018 |
| The data support the contention that prolonged antagonism of glucosylceramide synthase (GCS)in the central nervous system (CNS)can affect alpha-synuclein processing and improve behavioral outcomes. Hence, inhibition of GCS represents a disease-modifying therapeutic strategy for GBA-related synucleinopathies and conceivably for certain forms of sporadic disease | Glucosylceramide synthase inhibition alleviates aberrations in synucleinopathy models.
Sardi SP, Viel C, Clarke J, Treleaven CM, Richards AM, Park H, Olszewski MA, Dodge JC, Marshall J, Makino E, Wang B, Sidman RL, Cheng SH, Shihabuddin LS., Free PMC Article | 04/21/2018 |
| These results indicate that Gba1 deficiency enhances neuronal vulnerability to neurodegenerative processes triggered by increased alpha-synuclein expression. | The L444P Gba1 mutation enhances alpha-synuclein induced loss of nigral dopaminergic neurons in mice.
Migdalska-Richards A, Wegrzynowicz M, Rusconi R, Deangeli G, Di Monte DA, Spillantini MG, Schapira AHV., Free PMC Article | 10/7/2017 |
| This study demonstrated that the gba1 deficiency mice showed gene regulation expression of the type I interferon. | Induction of the type I interferon response in neurological forms of Gaucher disease.
Vitner EB, Farfel-Becker T, Ferreira NS, Leshkowitz D, Sharma P, Lang KS, Futerman AH., Free PMC Article | 09/30/2017 |