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Neuron. 2015 Mar 4;85(5):901-10. doi: 10.1016/j.neuron.2014.12.063.

From intrinsic firing properties to selective neuronal vulnerability in neurodegenerative diseases.

Author information

1
Friedrich Miescher Institut for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
2
Friedrich Miescher Institut for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland. Electronic address: caroni@fmi.ch.

Abstract

Neurodegenerative diseases (NDDs) involve years of gradual preclinical progression. It is widely anticipated that in order to be effective, treatments should target early stages of disease, but we lack conceptual frameworks to identify and treat early manifestations relevant to disease progression. Here we discuss evidence that a focus on physiological features of neuronal subpopulations most vulnerable to NDDs, and how those features are affected in disease, points to signaling pathways controlling excitation in selectively vulnerable neurons, and to mechanisms regulating calcium and energy homeostasis. These hypotheses could be tested in neuronal stress tests involving animal models or patient-derived iPS cells.

PMID:
25741719
DOI:
10.1016/j.neuron.2014.12.063
[Indexed for MEDLINE]
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