A5077753619- Parkinson's Disease Mechanisms and Treatments
- Nerve injury and regeneration
- Neurological disorders and treatments
- Nuclear Receptors and Signaling
- Alzheimer's disease research and treatments
- Genetic Neurodegenerative Diseases
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neuropharmacology Research
- Autism Spectrum Disorder Research
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA regulation and disease
- RNA Interference and Gene Delivery
- Neurological diseases and metabolism
- Neuroscience and Neural Engineering
- Virus-based gene therapy research
- Memory and Neural Mechanisms
- Mitochondrial Function and Pathology
- Prion Diseases and Protein Misfolding
- Dementia and Cognitive Impairment Research
- Botulinum Toxin and Related Neurological Disorders
- Biotin and Related Studies
- Pluripotent Stem Cells Research
- Signaling Pathways in Disease
- Cellular transport and secretion
- Pancreatic function and diabetes
Arizona State University
2021-2025
Rush University Medical Center
2012-2021
John Wiley & Sons (United States)
2017
Hudson Institute
2017
Anhui Medical University
2016
Jinzhou Medical University
2015
Taipei Medical University
2015
Texas Health Dallas
1997-2015
Penn Presbyterian Medical Center
1997-2015
Qinghai University
2010
Lentiviral delivery of glial cell line–derived neurotrophic factor (lenti-GDNF) was tested for its trophic effects upon degenerating nigrostriatal neurons in nonhuman primate models Parkinson's disease (PD). We injected lenti-GDNF into the striatum and substantia nigra nonlesioned aged rhesus monkeys or young adult treated 1 week prior with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Extensive GDNF expression anterograde retrograde transport seen all animals. In monkeys, augmented...
The pace of nigrostriatal degeneration, both with regards to striatal denervation and loss melanin tyrosine hydroxylase-positive neurons, is poorly understood especially early in the Parkinson's disease process. This study investigated extent degeneration patients at different durations from time diagnosis. Brains (n=28) post-diagnostic intervals 1-27 years normal elderly control subjects (n=9) were examined. Sections post-commissural putamen substantia nigra pars compacta processed for...
Layer II of the entorhinal cortex contains cells origin for perforant path, plays a critical role in memory processing, and consistently degenerates end-stage Alzheimer's disease. The extent to which neuron loss layer is related mild cognitive impairment without dementia has not been extensively investigated. We analyzed 29 participants who came autopsy from our ongoing longitudinal study aging composed religious clergy (Religious Orders Study). All individuals underwent detailed clinical...
The progressive loss of the nigrostriatal pathway is a distinguishing feature Parkinson's disease. As terminal field seems to precede cell body loss, we tested whether alterations axonal transport motor proteins would be early features in There was decline sporadic disease that preceded other well-known nigral cell-related pathology such as phenotypic downregulation dopamine. Reductions conventional kinesin levels dopaminergic markers (tyrosine hydroxylase) stages This reduction...
Abstract Background Nerve growth factor (NGF) is an endogenous neurotrophic‐factor protein with the potential to restore function and protect degenerating cholinergic neurons in Alzheimer's disease (AD), but safe effective delivery has proved unsuccessful. Methods Gene transfer, combined stereotactic surgery, offers a means solve long‐standing obstacles. An open‐label clinical trial evaluated safety tolerability, initial efficacy of three ascending doses genetically engineered gene‐therapy...
Abstract This report describes pathological changes within the grafted neurons of another patient with Parkinson's disease (PD) who died 14 years posttransplantation. Although numerous healthy appearing were present at this long‐term time point, some displayed Lewy bodies as evidenced by alpha‐synuclein, ubiquitin, and thioflavin‐S staining. Additionally, there was a general loss dopamine transporter‐immunoreactivity in neurons. Some cell tyrosine hydroxylase. These data support emerging...
The primate striatum contains tyrosine hydroxylase (TH)-immunoreactive (ir) neurons, the numbers of which are augmented after dopamine depletion. Glial cell line-derived neurotrophic factor (GDNF) strongly modulates viability and phenotypic expression ventral mesencephalic neurons. effect GDNF on TH-ir neurons intrinsic to has yet be investigated. In present study, stereological counts striatal in aged parkinsonian nonhuman primates revealed that delivered via a lentiviral vector (lenti-)...
In mammals, the transcription factor Nurr1 is expressed early in development and continues to be detectable throughout organism's lifetime. involved establishment maintenance of dopaminergic phenotype within specific central nervous system neuronal subpopulations including nigrostriatal dopamine system. This protein reduced over course normal aging, which a major risk for Parkinson's disease (PD). However, whether expression affected by PD has not been documented. The present study examined...
Nuclear receptor-related factor 1 (Nurr1), a member of the nuclear receptor superfamily, is associated with induction dopaminergic (DA) phenotypes in developing and mature midbrain neurons. It well established that nigrostriatal function decreases age. Whether age-related deficits DA phenotypic markers are alterations Nurr1 expression unknown. The present study found virtually all tyrosine hydroxylase-immunoreactive (TH-ir) neurons within young adult human substantia nigra were...
The clinical evaluation of neural transplantation as a potential treatment for Huntington's disease (HD) was initiated in an attempt to replace lost neurons and improve patient outcomes. Two 3 patients with HD reported here, who underwent containing striatal anlagen the striatum decade earlier, have demonstrated marginal transient benefits. Their brains were evaluated immunohistochemically electron microscopy markers projection interneurons, inflammatory cells, abnormal huntingtin protein,...
Abstract Background: AAV2‐neurturin (CERE‐120) is designed to deliver the neurotrophic‐factor, neurturin, striatum restore and protect degenerating nigrostriatal neurons in Parkinson's disease (PD). A common hypothesis that following expression striatum, neurotrophic‐factors like neurturin (NRTN) will be transported from terminals their cell bodies substantia nigra pars compacta (SNc). Methods: We tested this concept using immunohistochemistry, comparing bioactivity of brains PD patients...
The etiopathogenesis of sporadic Parkinson's disease (PD) remains elusive although mitochondrial dysfunction has long been implicated. Recent evidence revealed reduced expression peroxisome proliferator-activated receptor gamma coactivator−1 α (PGC−1α) and downstream regulated nuclear encoded respiratory complex genes in affected brain tissue from PD patients. We sought to determine whether epigenetic modification the PGC−1α gene could account for diminished expression. In substantia nigra...
Abstract Several studies have demonstrated that intrastriatal injections of fibrillar α-synuclein in rodent brain induced a Parkinson’s disease-like propagation Lewy body pathology with significant nigrostriatal neurodegeneration. This study evaluated the pathological features when exogenous preformed fibrils were injected into putamen non-human primates. Eight cynomolgus monkeys received unilateral intraputamen and four sham surgery. Monkeys assessed 123I-PE2I single-photon emission...
We observed Lewy pathology in healthy embryonic dopamine neurons implanted into the striatum of patients with advanced Parkinson's disease. In present study we examined temporal relationship between presence inflammation activated microglia and emergence α-synuclein pathology. Inflammation was all grafts at time points 18 months 16 years as determined by both CD45 TMEM119 staining. contrast, not detected months, only diffuse monomeric staining 4 years, aggregates were until 14–16 after...
Abstract We performed post-mortem studies on two patients with advanced Parkinson’s disease 8 and10 years following AAV2-neurturin (CERE120) gene therapy, the longest trophic factor therapy cases reported to date. CERE120 was delivered putamen bilaterally in one case (10 post-surgery), and plus substantia nigra second (8 post-surgery). In both there persistent, albeit limited, neurturin expression covering ∼3–12% of putamen. putamen, dense staining tyrosine hydroxylase-positive fibres...
Abstract While Parkinson’s disease remains clinically defined by cardinal motor symptoms resulting from nigrostriatal degeneration, it is now appreciated that the commonly consists of multiple pathologies, but unclear where these co-pathologies occur early in and whether they are responsible for degeneration. For past number years, we have been studying a well-characterized cohort subjects with impairment termed mild deficits. Motor deficits were determined on modified validated Unified...
Abstract Synucleinopathies are neurodegenerative diseases characterized by pathological inclusions called “Lewy pathology” (LP) that consist of aggregated alpha-synuclein predominantly phosphorylated at serine 129 (PSER129). Despite the importance for understanding disease, little is known about endogenous function PSER129 or why it accumulates in diseased brain. Here we conducted several observational studies using a sensitive tyramide signal amplification (TSA) technique to determine...