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Peptide Transport and Delivery into the Central Nervous System pp 101–123Cite as

Birkhäuser

Intracranial delivery of proteins and peptides as a therapy for neurodegenerative diseases

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Part of the book series: Progress in Drug Research ((PDR,volume 61))

Abstract

Parkinson’s disease (PD) is characterized by a progressive degeneration of the substantia nigra pars compacta dopamine neurons that innervate the striatum [1]. The loss of striatal dopamine and the consequent dysfunction of the nigrostriatal pathway lead to the cardinal symptoms of PD: resting tremor, cogwheel rigidity, bradykinesia (or difficulty to initiate movement) and loss of postural reflex. Current pharmacological treatment strategies for PD aim at replacing striatal dopamine using the dopamine precursor levodopa or dopamine receptor agonists, or both. Such treatments provide symptomatic relief, but do not slow or halt continued degeneration of nigral dopaminergic neurons. Therefore, interventions that could potentially slow or reverse the progression of neuronal degeneration would benefit PD patients. One such approach involves trophic factor administration. Trophic factors are proteins with enormous therapeutic potential in the treatment of neurodegenerative diseases. However, delivery of these proteins to the brain remains a challenge. Theoretically, a variety of different routes of administration could be used to deliver neurotrophic factors to the diseased brain, including intracranial (e.g. intraparenchymal), intranasal, intrathecal and parenteral (e.g. intravenous, subcutaneous or intramuscular) administration. Parenteral administration requires the drug to enter the brain from the systemic circulation by crossing the blood-brain barrier.

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Abbreviations

GDNF:

glial cell line-derived neurotrophic factor

GPI:

glycosyl-phosphatidylinositol

HVA:

homovanillic acid

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropiridine

MRI:

magnetic resonance imaging

O.D.:

outer diameter

PD:

Parkinson’s disease

TGF:

transforming growth factor

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Authors and Affiliations

  1. Department of Anatomy & Neurobiology and the Morris K. Udall Parkinson’s Disease Research Center of Excellence, University of Kentucky Medical Center, 305 Davis-Mills Bldg, Lexington, KY, 40536-0098, USA

    Richard Grondin, Zhiming Zhang, Yi Ai, Don M. Gash & Greg A. Gerhardt

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  1. Richard Grondin
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  2. Zhiming Zhang
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  3. Yi Ai
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  4. Don M. Gash
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  5. Greg A. Gerhardt
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Editors and Affiliations

  1. Department of Medicinal Chemistry, College of Pharmacy and The McKnight Brain Institute, University of Florida, 1600 S.W. Archer Road, Gainesville, FL, 32610-0497, USA

    Laszlo Prokai

  2. Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, 1600 S.W. Archer Road, Gainesville, FL, 32610-0267, USA

    Katalin Prokai-Tatrai

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Grondin, R., Zhang, Z., Ai, Y., Gash, D.M., Gerhardt, G.A. (2003). Intracranial delivery of proteins and peptides as a therapy for neurodegenerative diseases. In: Prokai, L., Prokai-Tatrai, K. (eds) Peptide Transport and Delivery into the Central Nervous System. Progress in Drug Research, vol 61. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8049-7_4

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  • DOI: https://doi.org/10.1007/978-3-0348-8049-7_4

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-9420-3

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