We used tryptophan fluorescence along with near- and farUV CD techniques to determine if there were any changes in the tertiary and secondary structures of the Wt proteins compared to the mutant proteins. The intrinsic fluorescence spectra indicated some differences between Wt and mutant proteins. The fluorescence intensity of aAR12A, aBR12A and Hsp27R12A increased,27%, 8% and 10%, respectively, compared to the corresponding Wt proteins. Moreover, the lmax of the tryptophan fluorescence spectra of the wild-type proteins did not alter due to the mutation. The changes in fluorescence intensity may reflect changes in the microenvironment of W9 and W16, which are located close to the mutation sites. The near-UV CD spectra of these three proteins agreed with our intrinsic fluorescence data. However, these changes in tryptophan fluorescence did not correlate with the changes in the chaperone function. While some studies showed a direct relationship between an increase in tryptophan fluorescence with improved chaperone function, others did not find such a relationship. miRNAs are abundantly expressed in the human brain and are essential for normal brain development and function. Experimental deletion of Dicer from neurons results in spine loss, apoptosis and functional deficits. Dicer deletion from astrocytes triggers seizures as well as a degenerative phenotype. Accordingly, altered miRNA expression may contribute to CNS pathologies and loss of Dicer and specific miRNAs, including miR133b and miR-9, has been reported in neurodegenerative diseases. Temporal lobe epilepsy is a common, chronic neurologic disorder characterized by recurrent spontaneous seizures which originate in brain structures such as the hippocampus. Hippocampal sclerosis is often present in Reversine patients with refractory TLE, comprising neuron loss and gliosis within the CA1, CA3, hilus/CA4, often accompanied by dispersion of the granule cell layer. Loss of neurons is less common in the neocortex of TLE patients. Dysregulation of genes affecting neurotransmission, gliosis, neuroinflammation and apoptosis has been proposed to underlie the pathogenesis of TLE with HS but our understanding of the mechanisms remains incomplete. Dicer is essential for production of most mature miRNAs and its loss from neurons or astrocytes results in miRNA down-regulation, neuronal dysfunction and apoptosis, seizures and cognitive deficits. Thus, the phenotype of Dicer deletion shares important commonalities with the hallmarks of TLE and its underlying pathophysiology. Altered miRNA expression has been suggested to be a causal factor in several CNS diseases but the present study is the first to both investigate miRNA biogenesis and profile miRNA expression in human TLE. We found a selective reduction in Dicer levels in tissue from TLE patients with severe HS. We also found Dicer levels were reduced in experimental TLE-HS. Since Dicer levels were normal in less sclerotic human TLE tissue, and are not changed after status epilepticus or brief non-harmful seizures, the loss of Dicer appears specific to TLE with HS. These findings represent a significant advance on previous work that showed dysregulation of miRNAs after seizures and in epilepsy. Given the pathological consequences of Dicer loss in brain we speculate that loss of Dicer may contribute to the pathogenesis of TLE-HS.