Article
Medicine, General & Internal
Tomas Kouba, Vojtech Illner, Jan Rusz
Summary: Early identification of Parkinson's disease is crucial for the development of neuroprotective therapies, but accurate biomarkers for prodromal PD are lacking. The vocal assessment of patients with isolated rapid eye movement sleep behaviour disorder (iRBD) and PD shows potential as a diagnostic and progressive biomarker. This study collects speech patterns from iRBD, early PD and control participants using a smartphone application and expects to find significant increase in PD-related speech disorders. Ethics approval has been obtained, and the study findings will be published and presented at scientific conferences.
Article
Behavioral Sciences
Ohnmar Hsam, Zacharias Kohl
Summary: Dysfunction of the serotonergic system is a significant characteristic in synucleinopathies, such as Parkinson disease, dementia with Lewy bodies, and Multiple system atrophy. Studies have shown that alterations in the serotonergic system are associated with non-motor symptoms, motor complications, and autonomic features of these diseases. Postmortem studies, animal models, and imaging techniques have contributed to understanding the pathophysiology of the serotonergic system, leading to potential drug targets. This review summarizes recent work that expands the knowledge of the serotonergic system and its relevance to synucleinopathies' pathophysiology.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Chiao-Yin Lee, Elisa Menozzi, Kai-Yin Chau, Anthony H. Schapira
Summary: The GBA1 and LRRK2 genes play important roles in Parkinson's disease by influencing the endolysosomal pathway and protein functions, leading to changes in pathophysiology.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Clinical Neurology
Jasmin Galper, Manisha Balwani, Stanley Fahn, Cheryl Waters, Lynne Krohn, Ziv Gan-Or, Nicolas Dzamko, Roy N. Alcalay
Summary: The study found that Parkinson's disease patients with biallelic pathogenic variants in GBA have elevated plasma levels of ferritin, CCL18, and MIP1 alpha, while these biomarkers were not elevated in heterozygous GBA carriers.
MOVEMENT DISORDERS
(2021)
Review
Biochemistry & Molecular Biology
Zuzanna Granek, Julia Barczuk, Natalia Siwecka, Wioletta Rozpedek-Kaminska, Ewa Kucharska, Ireneusz Majsterek
Summary: Alpha-synucleinopathies are neurodegenerative diseases characterized by abnormal accumulation of alpha-synuclein protein in neurons and glial cells. GBA1 mutations, which result in reduced enzymatic activity of beta-glucocerebrosidase (GCase), are a significant risk factor for developing Parkinson's disease and dementia with Lewy bodies. The mechanisms by which GCase affects alpha-synuclein aggregation are not well understood. This article discusses the potential interactions between alpha-synuclein and GCase and explores how GBA1 mutations may impact the progression of alpha-synucleinopathies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Casey L. Mahoney-Crane, Megha Viswanathan, Dreson Russell, Rachel A. C. Curtiss, Jennifer Freire, Sai Sumedha Bobba, Sean D. Coyle, Monika Kandebo, Lihang Yao, Bang -Lin Wan, Nathan G. Hatcher, Sean M. Smith, Jacob N. Marcus, Laura A. Volpicelli-Daley
Summary: The most common genetic risk factor for Parkinson's disease is heterozygous mutations GBA1, which leads to reduced glucocerebrosidase activity and accumulation of abnormal α-synuclein. This study used GBA1+/L444P mice to investigate its effects on lipid metabolism, synaptic protein expression, behavior, and α-syn inclusion formation.
JOURNAL OF NEUROSCIENCE
(2023)
Review
Pharmacology & Pharmacy
Mia Horowitz, Hila Braunstein, Ari Zimran, Shoshana Revel-Vilk, Ozlem Goker-Alpan
Summary: Lysosomes play a critical role in maintaining cellular homeostasis and dysfunction can lead to various diseases. Gaucher disease is a common lysosomal storage disorder that is associated with Parkinson's disease. Parkinson's disease is a neurodegenerative disorder characterized by abnormal aggregation of α-synuclein.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
Review
Pharmacology & Pharmacy
Elisa Menozzi, Marco Toffoli, Anthony H. V. Schapira
Summary: The GBA1 gene encodes the lysosomal enzyme glucocerebrosidase (GCase), which is involved in sphingolipid metabolism. Biallelic variants in GBA1 cause Gaucher disease (GD), a lysosomal storage disorder characterized by loss of GCase activity and aberrant intracellular accumulation of GCase substrates. Carriers of GBA1 variants have an increased risk of developing Parkinson disease (PD), with odds ratio ranging from 2.2 to 30 according to variant severity. GBA1 variants which do not cause GD in homozygosis can also increase PD risk.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Neurosciences
Matthew E. Gegg, Elisa Menozzi, Anthony H. V. Schapira
Summary: Dysfunction of the endolysosomal system is associated with the pathogenesis of Parkinson's disease (PD), and genetic variants in the GBA gene are a common risk factor. GCase deficiency in neurons and glia may contribute to PD by promoting the accumulation and spread of alpha-synuclein aggregates. Dysregulation of lipids, including sphingolipids, phospholipids, and cholesterol, as well as neuroinflammation and the interaction between GCase and LRRK2 protein, are also implicated in PD pathogenesis.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Chemistry, Medicinal
Tamaki Hoshikawa, Toru Watanabe, Makoto Kotake, Nathalie Tiberghien, Chi -kit Woo, Sian Lewis, Thomas Briston, Mumta Koglin, James M. Staddon, Ben Powney, Anthony H. V. Schapira, Andrew K. Takle
Summary: Glucocerebrosidase (GCase) is an enzyme encoded by the GBA1 gene, and its loss of function variants cause Gaucher disease (GD). Heterozygous variants of GBA1 are also the strongest common genetic risk factor for Parkinson's disease (PD). A compound with sub-micromolar activity was identified as a GCase pharmacological chaperone, and it was further optimized to a novel compound with improved ADME and physicochemical properties for investigating GCase pharmacology.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Clinical Neurology
Micol Avenali, Silvia Cerri, Gerardo Ongari, Cristina Ghezzi, Claudio Pacchetti, Cristina Tassorelli, Enza Maria Valente, Fabio Blandini
Summary: This study demonstrates that measuring biomarkers in peripheral blood mononuclear cells can clearly distinguish GBA-PD from non-mutated PD, with significant differences in alpha-synuclein levels, GCase activity, LIMP-2, and Saposin C levels between the two groups.
MOVEMENT DISORDERS
(2021)
Review
Clinical Neurology
Elisa Menozzi, Anthony H. V. Schapira, Fabio Blandini, Micol Avenali
Summary: The purpose of this review is to identify sensitive markers that can stratify the risk of Parkinson's disease (PD) in non-manifesting carriers of GBA1 and LRRK2 variants. Studies have shown that while the penetrance of PD is similar in GBA1 and LRRK2 variant carriers (10 - 30%), these individuals have distinct preclinical profiles. GBA1 variant carriers at higher risk of PD may exhibit prodromal symptoms such as hyposmia, increased levels of alpha-synuclein in peripheral blood mononuclear cells, and dopamine transporter abnormalities. LRRK2 variant carriers at higher risk of PD may show subtle motor abnormalities, higher exposure to certain environmental factors (non-steroidal anti-inflammatory drugs), and peripheral inflammatory profile. This information can assist clinicians in personalized screening and counseling, as well as aid researchers in developing predictive markers and disease-modifying treatments.
CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS
(2023)
Article
Neurosciences
Mantia Karampetsou, Kostas Vekrellis, Katerina Melachroinou
Summary: A large body of evidence suggests that the TGF-beta superfamily plays a regulatory role in the central nervous system. It is involved in embryonic brain development, adult brain tissue injury repair, and various processes related to Parkinson's disease, including the differentiation and synaptic function of dopaminergic neurons and the activation state of astrocytes and microglia. Studies using toxin models have explored the dopaminotrophic and protective effects of TGF-beta superfamily members.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Reito Nakamura, Ikumi Tomizawa, Atsushi Iwai, Tetsuo Ikeda, Kota Hirayama, Yung Wen Chiu, Takanobu Suzuki, Airi Tarutani, Tatsuo Mano, Atsushi Iwata, Tatsushi Toda, Youhei Sohma, Motomu Kanai, Yukiko Hori, Taisuke Tomita
Summary: Aggregation of alpha-synuclein into amyloid is a pathological hallmark of neurodegenerative disorders, and inhibiting this aggregation can be a potential therapeutic strategy. This study demonstrates that photo-oxygenation using a photocatalyst successfully inhibits alpha-synuclein aggregation by reducing its seeding ability. The oxidation of histidine residue in alpha-synuclein is found to be responsible for this inhibitory effect.
Article
Clinical Neurology
Mariana L. Laporta, S. Chandralekha Kruthiventi, Cole D. Stang, Emanuele Camerucci, David P. Martin, Toby N. Weingarten, Andrew C. Hanson, Darrell R. Schroeder, David O. Warner, Rodolfo Savica, Juraj Sprung
Summary: This study did not find a significant association between exposure to general anesthesia and the development of alpha-synucleinopathies.
PARKINSONISM & RELATED DISORDERS
(2021)