Anavex Life Sciences Corp. has announced that a publication in the current issue of scientific journal Neuropathology potentially extends the opportunity for ANAVEX PLUS to additional neurodegenerative diseases beyond Alzheimer’s.
The report demonstrates for the first time, evidenced by human brain autopsies, that the sigma-1 receptor (Sig-1R) is also involved in a family of neurodegenerative genetic disorders including Huntington’s disease (HD), dentatorubral-pallidoluysian atrophy (DRPLA), and spinocerebellar ataxia types 1, 2 and 3 (SCA1, SCA2, SCA3). They are caused by abnormal expansion of a polyglutamine stretch in each of the unrelated causative proteins. Sig-1R was consistently expressed and co-localized with neuronal nuclear inclusions in these polyglutamine diseases, confirming the implication of Sig-1R in cell survival in these neurodegenerative diseases.
Accumulation of misfolded proteins in brain cells is a common feature of most neurodegenerative diseases. Misfolded proteins may cause cell stress or cell dysfunction, leading to neuronal cell death. Sig-1R has previously been shown to facilitate the proper folding of newly synthesized proteins. It also prevents accumulation of misfolded proteins by consigning them to degradation, which is why the cell is able to survive. These actions confirm that increasing Sig-1R expression might play a key role in cellular survival in neurodegenerative diseases like Alzheimer’s.
According to the newly published report, neurodegenerative diseases characterized by neuronal nuclear inclusions apparently also utilize the Sig-1R-related degradation machinery as a pathway for the degradation of aberrant proteins. This indicates that Sig-1R expands its cellular protective reach and is even able to shuttle between the nucleus and the cytoplasm in order to prevent cell degeneration.
“We are encouraged by these recent findings that the sigma-1 receptor might promote critically needed cellular survival in additional neurodegenerative diseases beyond Alzheimer’s. This potentially expands the scope of indications for our drug candidate ANAVEX PLUS, which increases the expression of the sigma-1 receptor to help cells regain functionality and survive,” said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex.
The report, entitled “Accumulation of the sigma-1 receptor is common to neuronal nuclear inclusions in various neurodegenerative diseases,” was authored by Dr. Yasuo Miki, Department of Neuropathology, Institute of Brain Science, Hirosaki, Japan, and industry colleagues.
Accumulation of the sigma-1 receptor is common to neuronal nuclear inclusions in various neurodegenerative diseases, Yasuo Miki, Fumiaki Mori, Tomoya Kon, Kunikazu Tanji, Yasuko Toyoshima, Mari Yoshida, Hidenao Sasaki, Akiyoshi Kakita, Hitoshi Takahashi, Koichi Wakabayashi, Neuropathology – DOI: 10.1111/neup.12080