ABSTRACT
Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is rare and poorly understood and can affect a wide range of organ systems and is progressive in nature. Most commonly affecting the respiratory tract and kidneys, it has also been cited to affect the central nervous system (CNS) and skin. Proper and timely diagnosis will warrant appropriate treatment with slowing of disease progression. Our case illustrates a rare form of GPA with CNS and skin involvement that urges a wide differential for proper diagnosis.
ABSTRACT
Accumulation of α-synuclein (α-syn) into insoluble aggregates occurs in several related disorders collectively referred to as synucleinopathies. To date, studies have used neural stem cells (NSCs) to examine questions about α-syn propagation, but have overlooked the therapeutic potential of NSC transplantation to modulate cognition in disorders such as dementia with Lewy bodies or Parkinson's disease dementia. Here, we show that striatal transplantation of NSCs into aged α-syn transgenic mice significantly improves performance in multiple cognitive and motor domains. This recovery is associated with NSC expression of brain-derived neurotrophic factor (BDNF), which restores depleted levels and modulates dopaminergic and glutamatergic systems. Most importantly, transplantation of BDNF-depleted NSCs fails to improve behavior, whereas AAV-mediated BDNF delivery mimics the benefits of NSC transplantation, supporting a critical role for this neurotrophin in functional improvement. Thus, NSC transplantation could offer a promising approach to treat the understudied yet devastating cognitive components of many synucleinopathies.
