Nervous System Diseases Commons^™

Mammalian Target Of Rapamycin Cell Signaling Pathway In Phosphatase And Tensin Homolog Induced Kinase 1 Knockout Rat Model Of Familial Parkinson's Disease, Martha Helena Mortell

Theses and Dissertations--Medical Sciences

More than 10 million people are living with Parkinson’s disease (PD), one million of which are people in the United States. PD is the second most common age-related neurodegenerative disorder, after Alzheimer’s disease, and is characterized by the accumulation of a-synuclein aggregates and the degeneration of dopaminergic neurons. The loss of endogenous dopamine in PD brain accounts for the motor decline presented clinically in PD patients. Etiological factors of PD include oxidative damage and inflammation, although the detailed mechanisms remain unknown. Risk factors for PD include gender, age, environmental factors, and gene mutations.

The current thesis research employed phosphatase and …

Pre-Clinical Advancements In Biomarkers, Tools, And Therapeutics For A Metabolic Neurodegenerative Disease, Zoë Simmons

Theses and Dissertations--Molecular and Cellular Biochemistry

Glycogen is the storage form of glucose and a highly important substrate for cellular metabolism. Characterization of the enzymes and mechanisms of glycogen metabolism began over 70 years ago and over the last 20 years, a previously unknown protein called laforin has emerged as an important contributor to glycogen metabolism homeostasis. Multiple labs demonstrated that laforin is a glycogen phosphatase and mutations in the gene encoding laforin cause the formation of aberrant glycogen-like aggregates called Lafora bodies (LBs). LBs are cytoplasmic, water-insoluble aggregates that drive neurodegeneration and early death in Lafora disease (LD) patients. The direct relationship between mutated laforin, …

Autologous Peripheral Nerve Grafts To The Brain For The Treatment Of Parkinson's Disease, Andrew Welleford

Theses and Dissertations--Neuroscience

Parkinson’s disease (PD) is a disorder of the nervous system that causes problems with movement (motor symptoms) as well as other problems such as mood disorders, cognitive changes, sleep disorders, constipation, pain, and other non-motor symptoms. The severity of PD symptoms worsens over time as the disease progresses, and while there are treatments for the motor and some non-motor symptoms there is no known cure for PD. Thus there is a high demand for therapies to slow the progressive neurodegeneration observed in PD. Two clinical trials at the University of Kentucky College of Medicine (NCT02369003, NCT01833364) are currently underway that …

Histological And Behavioral Consequences Of Repeated Mild Traumatic Brain Injury In Mice, Amanda Nicholle Bolton Hall

Theses and Dissertations--Physiology

The majority of the estimated three million traumatic brain injuries that occur each year are classified as “mild” and do not require surgical intervention. However, debilitating symptoms such as difficulties focusing on tasks, anxiety, depression, and visual deficits can persist chronically after a mild traumatic brain injury (TBI) even if an individual appears “fine”. These symptoms have been observed to worsen or be prolonged when an individual has suffered multiple mild TBIs. To test the hypothesis that increasing the amount of time between head injuries can reduce the histopathological and behavioral consequences of repeated mild TBI, a mouse model of …

Investigating Therapeutic Options For Lafora Disease Using Structural Biology And Translational Methods, Amanda R. Sherwood

Theses and Dissertations--Molecular and Cellular Biochemistry

Lafora disease (LD) is a rare yet invariably fatal form of epilepsy characterized by progressive degeneration of the central nervous and motor systems and accumulation of insoluble glucans within cells. LD results from mutation of either the phosphatase laforin, an enzyme that dephosphorylates cellular glycogen, or the E3 ubiquitin ligase malin, the binding partner of laforin. Currently, there are no therapeutic options for LD, or reported methods by which the specific activity of glucan phosphatases such as laforin can be easily measured. To facilitate our translational studies, we developed an assay with which the glucan phosphatase activity of laforin as …