Mark S Moehle

Mark S Moehle,

Assistant Professor

Department: MD-PHARMACOLOGY / THERAPEUTICS
Business Phone: (352) 294-5571
Business Email: mark.moehle@ufl.edu

About Mark S Moehle

Teaching Profile

Courses Taught
2021-2024
GMS7593 Topics in Pharmacology and Toxicology
2021-2023
PAS5026 Pharmacotherapeu 2
2022
MDU4002 Introduction to Medical Science Seminar 2
2022-2024
DEN6262 Prin of Pharmacology
2023
GMS6022 Principles of Neurophysiology
2023-2024
BMS6020 Clinical Neuroscience
2023-2024
BMS6031 Foundations of Med
2024
GMS6009 Principles of Drug Action and Therapeutics

Research Profile

Visit moehlelab.org for the latest information on my lab!

The overarching goal of the Moehle Laboratory is to understand the cellular, molecular, and circuitry changes that underlie symptoms of neurological disorders. Using this deep understanding of changes to the brain in disease, we will be able to leverage these discoveries into novel therapeutic strategies for these diseases with large unmet clinical needs. Utilizing genetically, pharmacologically, and biochemically defined models of neurological disorders (such as dystonia, Parkinson’s Disease, and Dementias) we will perform cutting edge pharmacological, electrophysiological, behavioral, biochemical, and in vivo fiber photometry techniques to interrogate the cellular, molecular, and circuitry level changes in the central nervous system in these model systems. These studies have the possibility to make substantial advances in our understanding of brain wide changes in diseases such as Parkinson’s Disease, dystonia, and dementias as well as provide the pre-clinical rationale to direct larger drug discovery efforts for unique targets in these disorders.

Open Researcher and Contributor ID (ORCID)

0000-0002-8023-1313

Areas of Interest
  • Dystonia
  • Lewy Body Dementia
  • Movement Disorders
  • Muscarinic Acetylcholine Receptors
  • Parkinson’s disease

Publications

2023
Development of a Selective and High Affinity Radioligand, [3H]VU6013720, for the M4 Muscarinic Receptor.
Molecular pharmacology. 104(5):195-202 [DOI] 10.1124/molpharm.122.000643. [PMID] 37595966.
2023
Inhibition of LRRK2 kinase activity rescues deficits in striatal dopamine physiology in VPS35 p.D620N knock-in mice.
NPJ Parkinson's disease. 9(1) [DOI] 10.1038/s41531-023-00609-7. [PMID] 38110354.
2023
The muscarinic M4 acetylcholine receptor exacerbates symptoms of movement disorders
Biochemical Society Transactions. 51(2):691-702 [DOI] 10.1042/bst20220525.
2022
Cholinergic system changes in Parkinson’s disease: emerging therapeutic approaches.
The Lancet. Neurology. 21(4):381-392 [DOI] 10.1016/S1474-4422(21)00377-X. [PMID] 35131038.
2021
Discovery of the First Selective M4 Muscarinic Acetylcholine Receptor Antagonists with in Vivo Antiparkinsonian and Antidystonic Efficacy
ACS Pharmacology & Translational Science. 4(4):1306-1321 [DOI] 10.1021/acsptsci.0c00162. [PMID] 34423268.
2020
Activation of the mGlu1 metabotropic glutamate receptor has antipsychotic-like effects and is required for efficacy of M4 muscarinic receptor allosteric modulators
Molecular Psychiatry. 25(11):2786-2799 [DOI] 10.1038/s41380-018-0206-2. [PMID] 30116027.
2019
Roles of the M4 acetylcholine receptor in the basal ganglia and the treatment of movement disorders
Movement Disorders. 34(8):1089-1099 [DOI] 10.1002/mds.27740. [PMID] 31211471.
2017
Cholinergic Projections to the Substantia Nigra Pars Reticulata Inhibit Dopamine Modulation of Basal Ganglia through the M4 Muscarinic Receptor.
Neuron. 96(6):1358-1372.e4 [DOI] 10.1016/j.neuron.2017.12.008. [PMID] 29268098.
2017
Co-Activation of Metabotropic Glutamate Receptor 3 and Beta-Adrenergic Receptors Modulates Cyclic-AMP and Long-Term Potentiation, and Disrupts Memory Reconsolidation.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 42(13):2553-2566 [DOI] 10.1038/npp.2017.136. [PMID] 28664928.
2017
α-Synuclein fibril-induced inclusion spread in rats and mice correlates with dopaminergic Neurodegeneration.
Neurobiology of disease. 105:84-98 [DOI] 10.1016/j.nbd.2017.05.014. [PMID] 28576704.
2016
Urinary LRRK2 phosphorylation predicts parkinsonian phenotypes in G2019S LRRK2 carriers.
Neurology. 86(11):994-9 [DOI] 10.1212/WNL.0000000000002436. [PMID] 26865512.
2015
Allosteric activation of M4 muscarinic receptors improve behavioral and physiological alterations in early symptomatic YAC128 mice.
Proceedings of the National Academy of Sciences of the United States of America. 112(45):14078-83 [DOI] 10.1073/pnas.1512812112. [PMID] 26508634.
2015
Leucine-rich Repeat Kinase 2 (LRRK2) Pharmacological Inhibition Abates α-Synuclein Gene-induced Neurodegeneration.
The Journal of biological chemistry. 290(32):19433-44 [DOI] 10.1074/jbc.M115.660001. [PMID] 26078453.
2015
Leucine-rich repeat kinase 2 deficiency is protective in rhabdomyolysis-induced kidney injury.
Human molecular genetics. 24(14):4078-93 [DOI] 10.1093/hmg/ddv147. [PMID] 25904107.
2015
M1 and M2 immune activation in Parkinson’s Disease: Foe and ally?
Neuroscience. 302:59-73 [DOI] 10.1016/j.neuroscience.2014.11.018. [PMID] 25463515.
2015
The G2019S LRRK2 mutation increases myeloid cell chemotactic responses and enhances LRRK2 binding to actin-regulatory proteins.
Human molecular genetics. 24(15):4250-67 [DOI] 10.1093/hmg/ddv157. [PMID] 25926623.
2014
Abrogation of α-synuclein-mediated dopaminergic neurodegeneration in LRRK2-deficient rats.
Proceedings of the National Academy of Sciences of the United States of America. 111(25):9289-94 [DOI] 10.1073/pnas.1403215111. [PMID] 24927544.
2014
Differential LRRK2 expression in the cortex, striatum, and substantia nigra in transgenic and nontransgenic rodents.
The Journal of comparative neurology. 522(11):2465-80 [DOI] 10.1002/cne.23583. [PMID] 24633735.
2014
Unique functional and structural properties of the LRRK2 protein ATP-binding pocket.
The Journal of biological chemistry. 289(47):32937-51 [DOI] 10.1074/jbc.M114.602318. [PMID] 25228699.
2013
LRRK2 secretion in exosomes is regulated by 14-3-3.
Human molecular genetics. 22(24):4988-5000 [DOI] 10.1093/hmg/ddt346. [PMID] 23886663.
2012
LRRK2 inhibition attenuates microglial inflammatory responses.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 32(5):1602-11 [DOI] 10.1523/JNEUROSCI.5601-11.2012. [PMID] 22302802.
2012
Regional differences in expression of β-tubulin isoforms in schizophrenia.
Schizophrenia research. 135(1-3):181-6 [DOI] 10.1016/j.schres.2011.12.010. [PMID] 22264600.

Grants

Aug 2023 ACTIVE
Human alpha-synuclein templated pathology disruption of M2 cortex to striatum synaptic transmission and motor behaviors in Parkinsons disease
Role: Principal Investigator
Funding: FOX FOU, MICHAEL J
Apr 2023 ACTIVE
Cholinergic Mechanisms in Lewy Body Dementia
Role: Principal Investigator
Funding: NATL INST OF HLTH NINDS
Sep 2022 ACTIVE
Pathophysiology of DYT1 dystonia: Targeted Mouse Models
Role: Co-Investigator
Funding: NATL INST OF HLTH NINDS
Jul 2022 ACTIVE
M5 modulators to treat or modify the motor symptoms of Parkinsons Disease
Role: Principal Investigator
Funding: FOX FOU, MICHAEL J
Mar 2021 – Feb 2024
M4 muscarinic acetylcholine receptor signaling as a potent regulator of motor deficits
Role: Principal Investigator
Funding: NATL INST OF HLTH NINDS
Jan 2021 – Dec 2021
Impact of aggregated a-synuclein on altering neuronal physiology and plasticity in vivo and ex vivo in relevant animal models of LBD
Role: Principal Investigator
Funding: UF FOUNDATION
Jul 2020 ACTIVE
Molecular Mechanisms of Hair Bundle Development and Maintenance
Role: Co-Investigator
Funding: NATL INST OF HLTH NIDCD
Jul 2015 – Jun 2022
Research Pharmacology IX
Role: Project Manager
Funding: UF FOUNDATION

Education

Postdoc
2015-2020 · Vanderbilt University
Ph.D.
2010-2015 · University of Alabama at Birmingham
B.S.
2006-2010 · Centenary College of Louisiana

Contact Details

Phones:
Business:
(352) 294-5571
Emails:
Addresses:
Business Mailing:
PO Box 100267
GAINESVILLE FL 32610