Neuromolecular imaging, a nanobiotechnology for Parkinson’s disease: advancing pharmacotherapy for personalized medicine

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• 作者：P. A. Broderick ; L. Wenning ; Y.-S. Li
• 关键词：α ; Synuclein ; Alzheimer’s disease ; Dorsal striatum ; Nanobiosensors ; Peptides ; Prions
• 刊名：Journal of Neural Transmission
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：124
• 期：1
• 页码：57-78
• 全文大小：
• 刊物类别：Medicine
• 刊物主题：Neurology; Psychiatry; Pharmacology/Toxicology; Neurosciences;
• 出版者：Springer Vienna
• ISSN：1435-1463
• 卷排序：124

文摘

Evaluating each patient and animal as its own control achieves personalized medicine, which honors the hippocratic philosophy, explaining that “it is far more important to know what person has the disease than what disease the person has.” Similarly, individualizing molecular signaling directly from the patient’s brain in real time is essential for providing prompt, patient-based treatment as dictated by the point of care. Fortunately, nanotechnology effectively treats many neurodegenerative diseases. In particular, the new medicinal frontier for the discovery of therapy for Parkinson’s disease is nanotechnology and nanobiotechnology. Indeed, the unique nanotechnology of neuromolecular imaging combined with the series of nanobiosensors enables continuous videotracking of molecular neurotransmitters in both the normal physiologic and disease states with long-term electrochemical operational stability. This nanobiotechnology is able to track a signal in real time with excellent temporal and spatial resolution directly from each patient’s brain to a computer as subjects are behaving during movement, normal and/or dysfunctional including prion-like Parkinson’s behavioral biometrics. Moreover, the molecular signaling performed by these nanobiosensors live streams directly online and originates from precise neuroanatomic brain sites such as, in this case, the dorsal striatum in basal ganglia. Thus, the nanobiotechnology studies discussed herein imaged neuromolecules with and without l-3,4-dihydroxyphenylalanine (l-DOPA) in dorsal striatal basal ganglia neurons. Parkinsonian and non-Parkinsonian animals were video-tracked, and images were readily seen on a laptop via a potentiostat using a semiderivative electrical circuit. Administered l-DOPA doses were 50 and 100 mg/kg intraperitoneally (ip); the same experimental paradigm was used to image and then contrast data. Results showed that the baseline release of biogenic amine molecules was significantly above detection limits in non-Parkinsonian animals. After administration of l-DOPA, biogenic amines significantly increased in these non-Parkinson’s animals. Nevertheless, it is intriguing to see that l-DOPA could not enable synaptic dopamine release in Parkinson’s animals, thereby demonstrating that biogenic amines are biomarkers for Parkinson’s disease. Biomarkers are biochemical, genetic, or molecular measures of biological reactions. Importantly, there were other significant biomarkers present in Parkinsonian animals and absent in non-Parkinsonian animals; these were peptide neurotransmitters that include dynorphin and somatostatin in the brain with detection limits of 40 nM for dynorphin and 37 nM for somatostatin (see Table 1). Furthermore, l-DOPA significantly increased these peptide biomarkers, dynorphin and somatostatin, in Parkinson’s animals. Targeting biomarkers enables new diagnostic devices and treatments for Parkinson’s disease through nanotechnology and nanobiotechnology.