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Volume 8 Journal of Alzheimers Disease & Parkinsonism
ISSN: 2161-0460 Vascular Dementia 2018
February 22-23, 2018
Page 23
Notes:
conferenceseries.com
10th International Conference on
February 22-23, 2018 | Paris, France
Vascular Dementia
Markku Kurkinen, J Alzheimers Dis Parkinsonism 2018, Volume 8
DOI: 10.4172/2161-0460-C1-035
Alzheimer’s drug discovery: Targeting astrocyte synaptic glutamate uptake
According to the amyloid hypothesis, Alzheimer dementia begins in the brain with Aβ peptides accumulation and amyloid
formation. However, clinical drug trials targeting Aβ peptides and brain amyloid have failed to help anybody living with
Alzheimer. Instead of repeating similar trials and errors of 25 years, we have to discover novel drug targets and better our
research to prevent and treat Alzheimer. Glutamate is the synaptic signaling molecule of neurons. As soon as the glutamate
signaling starts it is stopped in 0.1-2 ms by astrocytes, which take up and clear glutamate from synapses. This prevents glutamate
neurotoxicity causing synapse loss and neuron cell death. Astrocytes make EAAT2 (excitatory amino acid transporter-2), the
major glutamate transporter and 1% of brain protein. In Alzheimer dementia, astrocytes are impaired in glutamate uptake. In
experimental mouse models of Alzheimer, increasing EAAT2 expression slows dementia progression. To discover drugs that
can activate EAAT2 in glutamate uptake; we describe a simple assay that targets the EAAT2 protein reconstituted in liposomes
and measures glutamate uptake with Oxonol VI red light. By directly targeting the EAAT2 protein, the assay should limit ‘off-
targeting’ of drugs and adverse events, which are the main problems in Alzheimer’s drug discovery and clinical development.
We may have to screen a million or more drugs, chemical compounds and natural products, before we find what we are looking
for. We believe our drug assay of liposome glutamate uptake, in a high-throughput screening (HTS) format, can do exactly that.
For efficacy, specificity and safety, the EAAT2 activating drugs are studied in an experimental C. elegans model of Alzheimer.
Biography
Markku Kurkinen has completed his PhD in 1979 at University of Helsinki, Finland and Post-doctoral studies from 1980-1983 at Imperial Cancer Research Fund, Mill
Hill, London, UK. He was an Assistant Professor from 1984-1986 at Rutgers Medical School, Piscataway, New Jersey, USA; Associate Professor from 1986-1992, and
Division Chief, Connective Tissue Research, Robert Wood Johnson Medical School, Piscataway, New Jersey, USA. He is a Professor at Wayne State University School
of Medicine, Detroit, Michigan, USA. He has published more than 100 papers, reviews and book chapters.
Markku Kurkinen
Wayne State University, USA