Neuronal Networks and Therapeutics in Neurodegenerative Disorders

Role of Ash1l in Tourette syndrome and other neurodevelopmental disorders

“…Therefore, we might construct a common framework which links the changes in the connectome among these diseases, placing them into a cross‐diseases environment that might disclose the common biological mechanisms and explain the overlapped symptomatology and shared developmental and genetic mechanisms. We further postulate that Ash1l may be located in the epicenter of the shared networks of connectional co‐substrates in multiple neuropsychiatric disorders virtually linked (Cauda et al., 2015; Crossley et al, 2014; Lakraj et al., 2014; Taniguchi & Moore, 2014; van der Heuvel & Sporns, 2019).…”

“…TS, ASD, ADHD, and SCZ, with overlapping behavioral phenotypes, are hereditary diseases with complex genetic etiologies (de Lacy & King, 2013; Harrison & Weinberger, 2005; Penzes et al, 2011; Rapoport et al., 2009), showing that multiple susceptible genes may work together to trigger disease onset along different nodes of a common pathway or network (Lakraj et al., 2014). Meta‐analysis studies identified 109 loci with pleiotropic effects, including Ash1l , associated with TS and co‐occurrence with psychiatric disorders (Brinkmeier et al., 2015; Lee et al., 2019).…”

“…In a neuropathological context, functional magnetic resonance imaging (fMRI) studies have unanimously reported abnormalities of long‐distance “underconnectivity” with short‐range “overconnectivity” in TS, ASD, ADHD, and SCZ patients (Cauda et al., 2015; Faundes et al., 2018; Kern et al., 2015; Lakraj et al., 2014; Lerner et al., 2012; Martino et al., 2018; Sahin & Sur, 2015; Vissers et al., 2012) that correlate with symptom severity (Cauda et al., 2015; Faundes et al., 2018; Kern et al., 2015; Lakraj et al., 2014; Lerner et al., 2012; Martino et al., 2018; Sahin & Sur, 2015; Vissers et al., 2012). The similarity in connectivity abnormalities in these disorders indicates a shared final pathway, providing further support for a common brain connectome and mis‐wired neural circuits in these disorders (Church et al., 2009; Kern et al., 2015; Vissers et al., 2012).…”