AANS Neurosurgeon | Volume 29, Number 2, 2020


Rethinking Neurodegenerative Disease Treatment: Target Multiple Pathological Proteins, Not Just One

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Penn study finds multiple ‘proteinopathies’ present in most neurodegenerative diseases, expanding treatment to target more of them may prove successful

Nearly all major neurodegenerative diseases – from Alzheimer’s to Parkinson’s – are defined and diagnosed by the presence of one of four proteins that have gone rogue: tau, amyloid-beta (A?), alpha-synuclein (?-syn), or TDP-43. As such, investigational drugs and studies aimed at preventing or slowing the disease often hone in on just one of these respective proteins. However, targeting multiple proteins—known as “proteinopathies”—at once may be the real key, according to a recent study published by Penn Medicine researchers. 

These so-called “proteinopathies”—misfolded proteins that accumulate and destroy neurons—co-exist in varying degrees across all of the different neurodegenerative disorders and may instigate each other to drive disease severity in many aging patients. The prevalence of these co-pathologies suggests that each disease may ultimately require combination therapy targeting multiple disease proteins, and not just a single therapy, in patients with both early and later-stage disease.

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