Delving into the Latest Updates on PAANIB-1 with Synapse

Overview

Basic Info

Drug Type

Chemical drugs

Synonyms-

Target

MIF

Action

inhibitors

Mechanism

MIF inhibitors(Macrophage migration inhibitory factor inhibitors)

Therapeutic Areas

Nervous System DiseasesEndocrinology and Metabolic Disease

Active Indication

Parkinson Disease

Inactive Indication-

Originator Organization

The Johns Hopkins University

Active Organization

The Johns Hopkins University

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Author: Song, Jae-Jin ; Chang, Sohyun ; Peng, Hanjing ; Chou, Shih-Ching ; Kam, Tae-In ; Mehrabani-Tabari, Amir A ; Choi, YuRee ; Karuppagounder, Senthilkumar S ; Park, Hyejin ; Dawson, Valina L ; Umanah, George K ; Rao, A V Subba ; Kim, Hyunhee ; Yin, Xiling ; Aggarwal, Akanksha ; Byun, Jiyoung ; Liu, Jun O ; Dawson, Ted M

Parthanatos-associated apoptosis-inducing factor (AIF) nuclease (PAAN), also known as macrophage migration inhibitor factor (MIF), is a member of the PD-D/E(X)K nucleases that acts as a final executioner in parthanatos. PAAN's role in Parkinson's disease (PD) and whether it is amenable to chemical inhibition is not known. Here, we show that neurodegeneration induced by pathologic α-synuclein (α-syn) occurs via PAAN/MIF nuclease activity. Genetic depletion of PAAN/MIF and a mutant lacking nuclease activity prevent the loss of dopaminergic neurons and behavioral deficits in the α-syn preformed fibril (PFF) mouse model of sporadic PD. Compound screening led to the identification of PAANIB-1, a brain-penetrant PAAN/MIF nuclease inhibitor that prevents neurodegeneration induced by α-syn PFF, AAV-α-syn overexpression, or MPTP intoxication in vivo. Our findings could have broad relevance in human pathologies where parthanatos plays a role in the development of cell death inhibitors targeting the druggable PAAN/MIF nuclease.

100 Deals associated with PAANIB-1

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