LRRK2, GBA and their interaction in the regulation of autophagy: implications on therapeutics in Parkinson's disease

Cross-talks among GBA mutations, glucocerebrosidase, and α-synuclein in GBA-associated Parkinson’s disease and their targeted therapeutic approaches: a comprehensive review

(2021) Tapan Behl et al.   Translational Neurodegeneration

Association of Dual LRRK2 G2019S and GBA Variations With Parkinson Disease Progression

(2021) Roberto A. Ortega et al.   JAMA Network Open

Targeting of Lysosomal Pathway Genes for Parkinson's Disease Modification: Insights From Cellular and Animal Models

(2021) Tetsuro Abe et al.   Frontiers in Neurology

A novel glucosylceramide synthase inhibitor attenuates alpha synuclein pathology and lysosomal dysfunction in preclinical models of synucleinopathy

(2021) Mali Cosden et al.   NEUROBIOLOGY OF DISEASE

Autophagy in Parkinson's Disease

(2020) Xu Hou et al.   JOURNAL OF MOLECULAR BIOLOGY

Precision medicine in Parkinson’s disease: emerging treatments for genetic Parkinson’s disease

(2020) Susanne A. Schneider et al.   JOURNAL OF NEUROLOGY

Lysosome and Inflammatory Defects in GBA1 ‐Mutant Astrocytes Are Normalized by LRRK2 Inhibition

(2020) Anwesha Sanyal et al.   MOVEMENT DISORDERS

Ambroxol for the Treatment of Patients With Parkinson Disease With and Without Glucocerebrosidase Gene Mutations

(2020) Stephen Mullin et al.   JAMA Neurology

Impact of GBA1 variants on long-term clinical progression and mortality in incident Parkinson’s disease

(2020) Thomas B Stoker et al.   JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY

A Possible Modifying Effect of the G2019S Mutation in the LRRK2 Gene on GBA Parkinson's Disease

(2020) Nurit Omer et al.   MOVEMENT DISORDERS

LRRK2 inhibitors induce reversible changes in nonhuman primate lungs without measurable pulmonary deficits

(2020) Marco A. S. Baptista et al.   Science Translational Medicine

LRRK2 Kinase Inhibition Rescues Deficits in Lysosome Function Due to Heterozygous GBA1 Expression in Human iPSC-Derived Neurons

(2020) Anwesha Sanyal et al.   Frontiers in Neuroscience

“LRRK2: Autophagy and Lysosomal Activity”

(2020) Marta Madureira et al.   Frontiers in Neuroscience

Kinase inhibition of G2019S-LRRK2 enhances autolysosome formation and function to reduce endogenous alpha-synuclein intracellular inclusions

(2020) Julia Obergasteiger et al.   Cell Death Discovery

Structure of LRRK2 in Parkinson’s disease and model for microtubule interaction

(2020) C. K. Deniston et al.   NATURE

Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Oral Venglustat in Healthy Volunteers

(2020) M. Judith Peterschmitt et al.   Clinical Pharmacology in Drug Development

Mitochondrial Dysfunction and Mitophagy in Parkinson’s Disease: From Mechanism to Therapy

(2020) Ana Belen Malpartida et al.   TRENDS IN BIOCHEMICAL SCIENCES

Efficacy of Nilotinib in Patients With Moderately Advanced Parkinson Disease

(2020) Tanya Simuni et al.   JAMA Neurology

Age-dependent accumulation of oligomeric SNCA/α-synuclein from impaired degradation in mutant LRRK2 knockin mouse model of Parkinson disease: role for therapeutic activation of chaperone-mediated autophagy (CMA)

(2019) Philip Wing-Lok Ho et al.   Autophagy

LRRK2 interacts with the vacuolar-type H+-ATPase pump a1 subunit to regulate lysosomal function

(2019) Rebecca Wallings et al.   HUMAN MOLECULAR GENETICS

GBA, Gaucher Disease, and Parkinson’s Disease: From Genetic to Clinic to New Therapeutic Approaches

(2019) Giulietta M. Riboldi et al.   Cells

Recent Developments in LRRK2-Targeted Therapy for Parkinson’s Disease

(2019) Ye Zhao et al.   DRUGS

Glucocerebrosidase and its relevance to Parkinson disease

(2019) Jenny Do et al.   Molecular Neurodegeneration

Neurorestorative effects of sub-chronic administration of ambroxol in rodent model of Parkinson’s disease

(2019) Akanksha Mishra et al.   NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY

Revisiting the non-Gaucher-GBA-E326K carrier state: Is it sufficient to increase Parkinson's disease risk?

(2019) Orly Goldstein et al.   MOLECULAR GENETICS AND METABOLISM

Stress-Induced Cellular Clearance Is Mediated by the SNARE Protein ykt6 and Disrupted by α-Synuclein

(2019) Leah K. Cuddy et al.   NEURON

LRRK2 kinase activity regulates lysosomal glucocerebrosidase in neurons derived from Parkinson’s disease patients

(2019) Daniel Ysselstein et al.   Nature Communications

Mutant LRRK2 mediates peripheral and central immune responses leading to neurodegeneration in vivo

(2018) Elena Kozina et al.   BRAIN

Familial knockin mutation of LRRK2 causes lysosomal dysfunction and accumulation of endogenous insoluble α-synuclein in neurons

(2018) Jason Schapansky et al.   NEUROBIOLOGY OF DISEASE

The Changing Landscape of Parkinson Epidemiologic Research

(2018) Honglei Chen   Journal of Parkinsons Disease

Mitochondrial Dysfunction and Mitophagy Defect Triggered by Heterozygous GBA Mutations

(2018) Hongyu Li et al.   Autophagy

Path mediation analysis reveals GBA impacts Lewy body disease status by increasing α-synuclein levels

(2018) Anna Lisa Gündner et al.   NEUROBIOLOGY OF DISEASE

LRRK2 and its substrate Rab GTPases are sequentially targeted onto stressed lysosomes and maintain their homeostasis

(2018) Tomoya Eguchi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

LRRK2 activation in idiopathic Parkinson’s disease

(2018) Roberto Di Maio et al.   Science Translational Medicine

LRRK2 kinase regulates α-synuclein propagation via RAB35 phosphorylation

(2018) Eun-Jin Bae et al.   Nature Communications

Carriers of both GBA and LRRK2 mutations, compared to carriers of either, in Parkinson's disease: Risk estimates and genotype-phenotype correlations

(2018) Gilad Yahalom et al.   PARKINSONISM & RELATED DISORDERS

GBA mutations in Parkinson disease: earlier death but similar neuropathological features

(2017) C. H. Adler et al.   EUROPEAN JOURNAL OF NEUROLOGY

Clinical profiles associated with LRRK2 and GBA mutations in Brazilians with Parkinson's disease

(2017) Camilla P. da Silva et al.   JOURNAL OF THE NEUROLOGICAL SCIENCES

A “dose” effect of mutations in the GBA gene on Parkinson's disease phenotype

(2017) Avner Thaler et al.   PARKINSONISM & RELATED DISORDERS

Glucosylceramide synthase inhibition alleviates aberrations in synucleinopathy models

(2017) S. Pablo Sardi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Combined LRRK2 mutation, aging and chronic low dose oral rotenone as a model of Parkinson’s disease

(2017) Hui-Fang Liu et al.   Scientific Reports

Ambroxol effects in glucocerebrosidase and α-synuclein transgenic mice

(2016) Anna Migdalska-Richards et al.   ANNALS OF NEUROLOGY

Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's

(2016) Ganqiang Liu et al.   ANNALS OF NEUROLOGY

Survival and dementia inGBA-associated Parkinson's disease: The mutation matters

(2016) Roberto Cilia et al.   ANNALS OF NEUROLOGY

First model of dimeric LRRK2: the challenge of unrevealing the structure of a multidomain Parkinson's-associated protein

(2016) G. Guaitoli et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

Geniposide reduces α-synuclein by blocking microRNA-21/lysosome-associated membrane protein 2A interaction in Parkinson disease models

(2016) Chunhe Su et al.   BRAIN RESEARCH

Autophagic lysosome reformation dysfunction in glucocerebrosidase deficient cells: relevance to Parkinson disease

(2016) Joana Magalhaes et al.   HUMAN MOLECULAR GENETICS

Neuropsychiatric characteristics of GBA-associated Parkinson disease

(2016) Matthew Swan et al.   JOURNAL OF THE NEUROLOGICAL SCIENCES

Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases

(2016) Martin Steger et al.   eLife

ER Stress and Autophagic Perturbations Lead to Elevated Extracellular α-Synuclein in GBA-N370S Parkinson's iPSC-Derived Dopamine Neurons

(2016) Hugo J.R. Fernandes et al.   Stem Cell Reports

Genetic perspective on the role of the autophagy-lysosome pathway in Parkinson disease

(2015) Ziv Gan-Or et al.   Autophagy

Glucocerebrosidase activity in Parkinson’s disease with and withoutGBAmutations

(2015) Roy N. Alcalay et al.   BRAIN

Selective loss of glucocerebrosidase activity in sporadic Parkinson’s disease and dementia with Lewy bodies

(2015) Davide Chiasserini et al.   Molecular Neurodegeneration

Cognitive profile ofLRRK2-related Parkinson's disease

(2015) Sindhu Srivatsal et al.   MOVEMENT DISORDERS

Impact of glucocerebrosidase mutations on motor and nonmotor complications in Parkinson's disease

(2015) Tomoko Oeda et al.   NEUROBIOLOGY OF AGING

Ambroxol-induced rescue of defective glucocerebrosidase is associated with increased LIMP-2 and saposin C levels in GBA1 mutant Parkinson's disease cells

(2015) Giulia Ambrosi et al.   NEUROBIOLOGY OF DISEASE

Differential effects of severe vs mild GBA mutations on Parkinson disease

(2015) Z. Gan-Or et al.   NEUROLOGY

Alzheimer's and Parkinson's diseases: The prion concept in relation to assembled A , tau, and  -synuclein

(2015) M. Goedert   SCIENCE

Mitochondrial dysfunction and mitophagy in Parkinson's: from familial to sporadic disease

(2015) Brent J. Ryan et al.   TRENDS IN BIOCHEMICAL SCIENCES

Reduced glucocerebrosidase is associated with increased α-synuclein in sporadic Parkinson’s disease

(2014) Karen E. Murphy et al.   BRAIN

Ambroxol improves lysosomal biochemistry in glucocerebrosidase mutation-linked Parkinson disease cells

(2014) Alisdair McNeill et al.   BRAIN

Motor phenotype of LRRK2-associated Parkinson's disease: A tunisian longitudinal study

(2014) Fatma Nabli et al.   MOVEMENT DISORDERS

GBA-associated Parkinson's disease: Reduced survival and more rapid progression in a prospective longitudinal study

(2014) Kathrin Brockmann et al.   MOVEMENT DISORDERS

Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease

(2014) Mike A Nalls et al.   NATURE GENETICS

iPSC-derived neurons from GBA1-associated Parkinson’s disease patients show autophagic defects and impaired calcium homeostasis

(2014) David C. Schöndorf et al.   Nature Communications

LRRK2 R1441G mice are more liable to dopamine depletion and locomotor inactivity

(2014) Hui-Fang Liu et al.   Annals of Clinical and Translational Neurology

Nilotinib reverses loss of dopamine neurons and improves motor behavior via autophagic degradation of  -synuclein in Parkinson's disease models

(2013) M. L. Hebron et al.   HUMAN MOLECULAR GENETICS

Parkinson disease phenotype in Ashkenazi jews with and withoutLRRK2G2019S mutations

(2013) Roy N. Alcalay et al.   MOVEMENT DISORDERS

Interplay of LRRK2 with chaperone-mediated autophagy

(2013) Samantha J Orenstein et al.   NATURE NEUROSCIENCE

A comparative study of Parkinson's disease and leucine-rich repeat kinase 2 p.G2019S parkinsonism

(2013) Joanne Trinh et al.   NEUROBIOLOGY OF AGING

RAB7L1 Interacts with LRRK2 to Modify Intraneuronal Protein Sorting and Parkinson’s Disease Risk

(2013) David A. MacLeod et al.   NEURON

Glucocerebrosidase deficiency in substantia nigra of parkinson disease brains

(2012) Matthew E. Gegg et al.   ANNALS OF NEUROLOGY

The LRRK2 G2019S mutant exacerbates basal autophagy through activation of the MEK/ERK pathway

(2012) José M. Bravo-San Pedro et al.   CELLULAR AND MOLECULAR LIFE SCIENCES

Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson's disease

(2012) Adriana Sánchez-Danés et al.   EMBO Molecular Medicine

A clinical and family history study of Parkinson's disease in heterozygousglucocerebrosidasemutation carriers

(2012) Alisdair McNeill et al.   JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY

The link between the GBA gene and parkinsonism

(2012) Ellen Sidransky et al.   LANCET NEUROLOGY

Cognitive performance of GBA mutation carriers with early-onset PD: The CORE-PD study

(2012) R. N. Alcalay et al.   NEUROLOGY

Ser1292 Autophosphorylation Is an Indicator of LRRK2 Kinase Activity and Contributes to the Cellular Effects of PD Mutations

(2012) Z. Sheng et al.   Science Translational Medicine

Microautophagy in mammalian cells: Revisiting a 40-year-old conundrum

(2011) Dalibor Mijaljica et al.   Autophagy

Gaucher Disease Glucocerebrosidase and α-Synuclein Form a Bidirectional Pathogenic Loop in Synucleinopathies

(2011) Joseph R. Mazzulli et al.   CELL

LRRK2 protein levels are determined by kinase function and are crucial for kidney and lung homeostasis in mice

(2011) Martin C. Herzig et al.   HUMAN MOLECULAR GENETICS

Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP

(2011) Patricia Gómez-Suaga et al.   HUMAN MOLECULAR GENETICS

The enigma of the E326K mutation in acid β-glucocerebrosidase

(2011) Mia Horowitz et al.   MOLECULAR GENETICS AND METABOLISM

AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1

(2011) Joungmok Kim et al.   NATURE CELL BIOLOGY

GBA-associated PD presents with nonmotor characteristics

(2011) K. Brockmann et al.   NEUROLOGY

Phenotype in parkinsonian and nonparkinsonian LRRK2 G2019S mutation carriers

(2011) C. Marras et al.   NEUROLOGY

Cognitive dysfunction in Tunisian LRRK2 associated Parkinson’s disease

(2011) Samia Ben Sassi et al.   PARKINSONISM & RELATED DISORDERS

TFEB Links Autophagy to Lysosomal Biogenesis

(2011) C. Settembre et al.   SCIENCE

Glucocerebrosidase is present in α-synuclein inclusions in Lewy body disorders

(2010) Ozlem Goker-Alpan et al.   ACTA NEUROPATHOLOGICA

Chaperone-Mediated Autophagy Markers in Parkinson Disease Brains

(2010) Lydia Alvarez-Erviti et al.   ARCHIVES OF NEUROLOGY

The incidence of Parkinsonism in patients with type 1 Gaucher disease: Data from the ICGG Gaucher Registry

(2010) Barry Rosenbloom et al.   BLOOD CELLS MOLECULES AND DISEASES

Pathogenic Lysosomal Depletion in Parkinson's Disease

(2010) B. Dehay et al.   JOURNAL OF NEUROSCIENCE

Termination of autophagy and reformation of lysosomes regulated by mTOR

(2010) Li Yu et al.   NATURE

LRRK2 G2019S mutation in Parkinson’s disease: A neuropsychological and neuropsychiatric study in a large Algerian cohort

(2010) Soreya Belarbi et al.   PARKINSONISM & RELATED DISORDERS

Chaperone-mediated autophagy: Molecular mechanisms and physiological relevance

(2010) Samantha J. Orenstein et al.   SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY

Alterations in lysosomal and proteasomal markers in Parkinson's disease: Relationship to alpha-synuclein inclusions

(2009) Yaping Chu et al.   NEUROBIOLOGY OF DISEASE

Role of autophagy in G2019S-LRRK2-associated neurite shortening in differentiated SH-SY5Y cells

(2008) Edward D. Plowey et al.   JOURNAL OF NEUROCHEMISTRY

Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study

(2008) Daniel G Healy et al.   LANCET NEUROLOGY

Autophagy fights disease through cellular self-digestion

(2008) Noboru Mizushima et al.   NATURE

Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset

(2008) W. C. Nichols et al.   NEUROLOGY

Genotype-phenotype correlations between GBA mutations and Parkinson disease risk and onset

(2008) Z. Gan-Or et al.   NEUROLOGY