8 Conclusion and Perspectives
Since the molecular cloning and mapping of the gene encoding the
γ2-regulatory energy-sensing subunit of AMPK in 2000 [11],
followed soon after by its causal link to a human inherited cardio-
myopathy with distinctive electrophysiological and histological fea-
tures, the literature pertaining toPRKAG2and AMPK’s function
in the heart has greatly increased. Reflecting the collective research
efforts of numerous scientists examining the AMPK pathway and
clinicians managing individuals with the PRKAG2 syndrome,
knowledge of disease mechanisms underlying the associated cardio-
myopathy has significantly advanced. These insights and future
studies hold promise not only to foster the development of specific
therapeutics for this monogenic disorder but more broadly to
inform understanding of the fundamental biology of the eukaryotic
cellular energy sensor and the potential for its targeting to treat
more prevalent, complex cardiac and metabolic diseases.Acknowledgments
The authors gratefully acknowledge Dr Kate Thomson and Karen
McGuire (Oxford Medical Genetics Laboratories) for their insight-
ful comments on the manuscript. This work was supported by
Starter Grants for Clinical Lecturers (supported by the Academy
of Medical Sciences, Wellcome Trust, Medical Research Council,
British Heart Foundation, Arthritis Research UK, and the Royal
College of Physicians and Diabetes UK) and an academic clinical
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