Review
Biochemistry & Molecular Biology
Pedro Ayuso, Felix Javier Jimenez-Jimenez, Javier Gomez-Tabales, Hortensia Alonso-Navarro, Elena Garcia-Martin, Jose A. G. Agundez
Summary: Parkinson's disease is a chronic neurodegenerative disorder affecting about 2% of the population over 65 years old. Current drug therapies aim to reduce symptoms and increase life expectancy, but there is variability in treatment response, possibly due to genetic factors. Pharmacogenomics has been suggested as a way to personalize drug therapy for Parkinson's disease.
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2023)
Article
Clinical Neurology
Emma McIntosh, Seamus Kent, Alastair Gray, Carl E. Clarke, Adrian Williams, Crispin Jenkinson, Natalie Ives, Smitaa Patel, Caroline Rick, Keith Wheatley, Richard Gray
Summary: The study found that initial treatment with levodopa is highly cost-effective compared with levodopa-sparing therapies, and monoamine oxidase type B inhibitors as initial levodopa-sparing therapy were more cost-effective, with similar quality-adjusted life-years but lower costs than dopamine agonists.
MOVEMENT DISORDERS
(2021)
Review
Cell Biology
Sachchida Nand Rai, Payal Singh, Ritu Varshney, Vivek K. Chaturvedi, Emanuel Vamanu, M. P. Singh, Brijesh Kumar Singh
Summary: Parkinson's disease is a debilitating brain disease with limited treatment options, highlighting the need for novel drug targets to improve patient health. Natural products may play a critical role in controlling the progression of Parkinson's disease.
NEURAL REGENERATION RESEARCH
(2021)
Review
Chemistry, Medicinal
Ashwani Kumar, Meenakshi Bhatia, Archana Kapoor, Parvin Kumar, Sunil Kumar, Sunil Kumar
Summary: Monoamine oxidase enzyme plays an essential role in brain function regulation, with its inhibitors showing potential in the treatment of neurological disorders. Reversible MAO inhibitors, which have been recently studied, may serve as safer alternatives to old monoamine oxidase inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Anjana Pathania, Rajnish Kumar, Rajat Sandhir
Summary: 3-Hydroxytyrosol (HXT) has the potential to inhibit MAO-B and maintain dopamine levels, thus serving as a candidate for the treatment of Parkinson's disease.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Clinical Neurology
Peter Riederer, Reinhard Horowski
Summary: Dopamine, initially considered an intermediate in noradrenaline synthesis, was later found to be a neurotransmitter and its depletion led to characteristic symptoms found in Parkinson's disease. Clinical researchers and physicians worldwide, especially Arvid Carlsson, played a crucial role in the breakthrough of L-DOPA therapy and the development of alternative therapies for Parkinson's disease, leading to the establishment of current Parkinson's disease therapy.
JOURNAL OF NEURAL TRANSMISSION
(2023)
Review
Pharmacology & Pharmacy
Peter Kempster, Andrew Ma
Summary: A large proportion of drugs for neurological disorders are derived from naturally occurring compounds, especially plant alkaloids. The treatment of Parkinson's disease has strong botanical origins, with plant-derived substances playing a significant role. The interaction between plant compounds and animal dopaminergic systems has deep evolutionary roots.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Neurosciences
Yu-Yan Tan, Peter Jenner, Sheng-Di Chen
Summary: This review discusses the effects of MAO-B inhibitors on motor and non-motor symptoms in PD patients, their mechanism of action, and the future development of MAO-B inhibitor therapy.
JOURNAL OF PARKINSONS DISEASE
(2022)
Article
Chemistry, Medicinal
Chao Yi, Xinchang Liu, Kangzhi Chen, Haiping Liang, Chuanfei Jin
Summary: A series of novel ((benzofuran-5-yl) methyl) pyrrolidine-2-carboxamide derivatives were designed, synthesized, and evaluated as MAO-B inhibitors. The most potent MAO-B inhibitor, (2S,4S)-4-fluoro-1-((2-(4-fluorophenyl) benzofuran-5-yl) methyl) pyrrolidine-2-carboxamide (C14), was obtained by cyclizing benzyl ether into a benzofuran ring (IC50 = 0.037 μM). C14 showed improved PK properties in rats and mice compared to previous candidates and safinamide, suggesting the essential role of the benzofuran moiety in enhancing PK properties. Additionally, C14 exhibited good metabolic stability, brain-blood barrier permeability, and favorable in vitro properties. Moreover, C14 significantly inhibited MAO-B in the mouse brain and showed potential efficacy for treating DA deficits in the MPTP-induced mouse model.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Qing Song, Guangjun Yu, Wei Li, Yidan Xu, Shiqin Cong, Xiuxiu Liu, Zhenghuai Tan, Yong Deng
Summary: A series of 6-benzyloxyphthalides were synthesized as potent inhibitors of monoamine oxidase B (MAO-B) with antioxidant and anti-neuroinflammatory activities. Compound 8f and 14a exhibited excellent selectivity towards MAO-B, moderate antioxidant activity, and in vitro antineuroinflammatory activities. In an in vivo mice model of Parkinson's disease, 8f and 14a showed better effects than safinamide in improving behavioral disorders and restoring dopamine content.
BIOORGANIC CHEMISTRY
(2022)
Article
Clinical Neurology
Roongroj Bhidayasiri, Michinori Koebis, Takanori Kamei, Takayuki Ishida, Ippei Suzuki, Jin Whan Cho, Shey-Lin Wu
Summary: This article is a post-hoc analysis study on the use of Safinamide in the treatment of patients with Parkinson's disease. It found that early responders to Safinamide had sustained response and significant improvements in OFF-time, UPDRS scores, and PDQ-39 scores throughout the treatment.
FRONTIERS IN NEUROLOGY
(2023)
Article
Pharmacology & Pharmacy
Qian Zhang, XiangTing Chen, FeiFei Chen, SiYuan Wen, ChangQing Zhou
Summary: Compared with levodopa, dopamine agonists (DAs) as initial treatment are associated with lower incidences of motor complications in early Parkinson's disease (PD). There is no strong evidence that a given DA is more potent in lower incidences of motor complications than another. We performed a network meta-analysis of levodopa versus DAs as monotherapy in early PD to assess the risk of motor complications.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Clinical Neurology
Diana A. Olszewska, Alfonso Fasano, Renato P. Munhoz, Carolina Candelaria Ramirez Gomez, Anthony E. Lang
Summary: This retrospective cohort study aimed to investigate the difference in the time between initial levodopa and dopamine agonist (DA) treatment and the development of disabling motor complications (MCs) in Parkinson's disease (PD) patients who underwent deep brain stimulation (DBS). The results showed no significant difference in the duration from the first treatment to DBS assessment or surgery between patients who received levodopa and those who received a DA.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Review
Virology
Yujie Sun, Wen Liu, Bing Luo
Summary: This review summarizes current research on how viral infections participate in the occurrence and development of human diseases through MAO. The viruses discussed in this review include hepatitis C virus, dengue virus, severe acute respiratory syndrome coronavirus 2, human immunodeficiency virus, Japanese encephalitis virus, Epstein-Barr virus, and human papillomavirus. The effects of MAO inhibitors such as phenelzine, clorgyline, selegiline, M-30, and isatin on viral infectious diseases are also described in this review. This information will provide new insights into the treatment and diagnosis of these viral diseases.
REVIEWS IN MEDICAL VIROLOGY
(2023)
Article
Chemistry, Medicinal
Badr Jismy, Abdelkarim El Qami, Anja Pislar, Rok Frlan, Janko Kos, Stanislav Gobec, Damijan Knez, Mohamed Abarbri
Summary: Heterotricyclic compounds exhibit potential as MAO inhibitors, particularly showing selective inhibition towards human MAO-B isoform. These derivatives are non-cytotoxic to neuroblastoma cells and have demonstrated protective effects against 6-hydroxydopamine-induced cell death.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Clinical Neurology
Daniel Weintraub, Dag Aarsland, Kallol Ray Chaudhuri, Roseanne D. Dobkin, Albert F. G. Leentjens, Mayela Rodriguez-Violante, Anette Schrag
Summary: Neuropsychiatric signs and symptoms are common in people with Parkinson's disease, and their underlying neurobiology is complex. Identifying risk factors and developing effective treatments require further research and specialized care models.
Article
Clinical Neurology
Thomas Guttuso, Daniel Sirica, Duygu Tosun, Robert Zivadinov, Ofer Pasternak, Daniel Weintraub, Francesca Baglio, Niels Bergsland
Summary: This study assessed the free water content changes in cognitive-relevant brain regions in early Parkinson's disease patients and their correlation with cognitive decline over time and baseline cognitive status. Results showed that free water was the most robust assessment modality for these outcomes and may assist in identifying cognition protective therapies in clinical trials.
MOVEMENT DISORDERS
(2022)
Article
Neurosciences
Hannah Staunton, Kim Kelly, Louise Newton, Mathias Leddin, Raul Rodriguez-Esteban, K. Ray Chaudhuri, Daniel Weintraub, Ronald B. Postuma, Pablo Martinez-Martin
Summary: This study aims to create a conceptual model of symptoms and impacts for individuals with early-stage Parkinson's disease (PD) by collecting qualitative data. The results show that the most frequently reported symptoms in early-stage PD include tremors, stiffness and rigidity, and fatigue, while the most commonly reported impacts include anxiety, eating and drinking, and exercise/sport and relationship with family/family life. The conceptual model can be used to guide researchers in developing and selecting patient-centered outcomes for clinical trials and inform future qualitative research and outcome development specifically for early-stage PD patients.
JOURNAL OF PARKINSONS DISEASE
(2022)
Article
Clinical Neurology
Maiko Takahashi, Jinsoo Koh, Shoko Yorozu, Yoshinori Kajimoto, Yoshiaki Nakayama, Mayumi Sakata, Masaaki Yasui, Yasuhiro Hiwatani, Daniel Weintraub, Hidefumi Ito
Summary: The present study validated the Japanese version of QUIP-RS and determined the characteristics of ICBs in Japan. The use of QUIP-RS-J enables standardized assessment of ICBs and can be used in clinical research.
PARKINSONS DISEASE
(2022)
Article
Clinical Neurology
Thomas F. Tropea, Teresa Waligorska, Sharon X. Xie, Ilya M. Nasrallah, Katheryn A. Q. Cousins, John Q. Trojanowski, Murray Grossman, David J. Irwin, Daniel Weintraub, Edward B. Lee, David A. Wolk, Alice S. Chen-Plotkin, Leslie M. Shaw
Summary: The objective of this study was to determine if plasma tau phosphorylated at threonine 181 (p-tau181) can distinguish Alzheimer's disease (AD) from normal cognition (NC) in adults, predict cognitive and functional decline, and validate findings in an external cohort. The results showed that plasma p-tau181 can accurately differentiate AD pathology from NC, and higher levels of p-tau181 are associated with faster cognitive and functional decline.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Article
Clinical Neurology
John L. Robinson, Sharon X. Xie, Daniel R. Baer, EunRan Suh, Vivianna M. Van Deerlin, Nicholas J. Loh, David J. Irwin, Corey T. McMillan, David A. Wolk, Alice Chen-Plotkin, Daniel Weintraub, Theresa Schuck, Virginia M. Y. Lee, John Q. Trojanowski, Edward B. Lee
Summary: In this retrospective study, the incidence of 10 pathologies in neurodegenerative disease (ND) and normal aging was examined, with up to seven pathologies observed concurrently resulting in 161 different combinations. The presence of multiple additive pathologies was associated with factors such as longer disease duration, clinical dementia, older age, and APOE e4 status.
Article
Clinical Neurology
Danielle S. Abraham, Thanh Phuong Pham Nguyen, Leah J. Blank, Dylan Thibault, Shelly L. Gray, Sean Hennessy, Charles E. Leonard, Daniel Weintraub, Allison W. Willis
Summary: This study examined the differential prescribing patterns between new and established treatments for common neurological conditions. Using data from a national sample of US commercially insured adults from 2005-2019, the study compared new users of recently approved medications for three conditions: diabetic peripheral neuropathy, Parkinson disease psychosis, and epilepsy. The results showed that newer medications were more frequently prescribed to individuals with prior treatment, suggesting potential bias in comparative effectiveness and safety studies. The study emphasizes the importance of reporting propensity score non-overlap in comparative studies involving newer medications and suggests methodological approaches to address channeling bias.
Article
Clinical Neurology
Katheryn A. Q. Cousins, David J. Irwin, Alice Chen-Plotkin, Leslie M. Shaw, Sanaz Arezoumandan, Edward B. Lee, David A. Wolk, Daniel Weintraub, Meredith Spindler, Andres Deik, Murray Grossman, Thomas F. Tropea
Summary: This study found that plasma GFAP may be sensitive to concomitant AD pathology in LBSD, especially accumulation of beta-amyloid plaques.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Article
Neurosciences
Kalpana M. Merchant, Tanya Simuni, Janel Fedler, Chelsea Caspell-Garcia, Michael Brumm, Kelly N. H. Nudelman, Elizabeth Tengstrandt, Frank Hsieh, Roy N. Alcalay, Christopher Coffey, Lana Chahine, Tatiana Foroud, Andrew Singleton, Daniel Weintraub, Samantha Hutten, Todd Sherer, Brit Mollenhauer, Andrew Siderowf, Caroline Tanner, Ken Marek
Summary: We quantified concentrations of three isoforms of BMP in different cohorts of Parkinson's disease patients and found that LRRK2 and GBA1 gene mutations were associated with elevated BMP levels. However, BMP is not a prognostic or disease progression biomarker.
NPJ PARKINSONS DISEASE
(2023)
Article
Clinical Neurology
Daniel Weintraub, Marina Picillo, Hyunkeun Ryan Cho, Chelsea Caspell-Garcia, Cornelis Blauwendraat, Ethan G. Brown, Lana M. Chahine, Christopher S. Coffey, Roseanne D. Dobkin, Tatiana Foroud, Doug Galasko, Karl Kieburtz, Kenneth Marek, Kalpana Merchant, Brit Mollenhauer, Kathleen L. Poston, Tanya Simuni, Andrew Siderowf, Andrew Singleton, John Seibyl, Caroline M. Tanner
Summary: This study used data from a multi-site, international, prospective cohort study to investigate the impact of dopamine system-related biomarkers on cognitive impairment in Parkinson's disease. The results showed that alterations in the dopamine system were associated with the development of cognitive impairment in Parkinson's disease. If confirmed causative, these findings suggest that the dopamine system is instrumental to cognitive health status throughout the disease course.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Clinical Neurology
Daniel Weintraub
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Hubert H. Fernandez, Daniel Weintraub, Eric Macklin, Irene Litvan, Michael A. Schwarzschild, Jamie Eberling, Aleksandar Videnovic, Christopher J. Kenney
Summary: In patients with Parkinson disease dementia (PDD), SYN120 did not improve cognition significantly but showed potential benefits in cognitive activities of daily living and apathy.
PARKINSONISM & RELATED DISORDERS
(2023)
Article
Clinical Neurology
Thanh Phuong Pham Nguyen, Shelly L. Gray, Craig W. Newcomb, Qing Liu, Ali G. Hamedani, Daniel Weintraub, Sean Hennessy, Allison W. Willis
Summary: This study found that there were no significant differences in medication prescriptions between Parkinson disease (PD) patients hospitalized for serious injury and those hospitalized for other reasons, indicating a missed opportunity to deprescribe high-risk medications during care transitions.
PARKINSONISM & RELATED DISORDERS
(2023)
Article
Clinical Neurology
Vindhya Koneru, Alberto J. Espay, Allan J. Cole, Daniel Weintraub, Kathleen Crist, Maria B. Pascual, William G. Ondo
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Daniel Weintraub
MOVEMENT DISORDERS
(2023)
