Astrocyte-mediated neuropil resistance (RP)

Astrocyte-mediated neuropil resistance (also known as parenchymal resistance or RP) is a physiological parameter that describes the hydraulic resistance to fluid flow within the brain's interstitial space [1, 10]. This resistance is primarily regulated by astrocytes, which control the volume and tortuosity of the extracellular space (ECS) through their perivascular endfeet and the expression of proteins such as Aquaporin-4 (AQP4) [2, 21]. In neurodegenerative diseases like Alzheimer's, increased neuropil resistance is associated with impaired glymphatic clearance of toxic proteins, including amyloid-beta and tau [12, 18]. Therapeutic candidates like ACX-02 and ACX-14 are designed to reduce this resistance, thereby facilitating the brain's natural waste-clearance mechanisms [1, 22]. By enhancing glymphatic flux, these interventions aim to reduce the accumulation of protein aggregates and slow the progression of cognitive decline [10, 23].

Other names

Parenchymal resistanceNeuropil resistanceBrain interstitial resistanceRP

Reduction of parenchymal resistance to facilitate glymphatic flow and enhance the clearance of neurotoxic proteins such as amyloid-beta and tau.