Provided herein are proteins, which are capable of being transported across the blood-brain barrier (BBB) and comprise sulfoglucosamine sulfohydrolase (SGSH) enzyme-Fc fusion polypeptides. Certain embodiments also provide methods of using such proteins to treat Sanfilippo syndrome A.

Provided herein are proteins, which are capable of being transported across the blood-brain barrier (BBB) and comprise sulfoglucosamine sulfohydrolase (SGSH) enzyme-Fc fusion polypeptides. Certain embodiments also provide methods of using such proteins to treat Sanfilippo syndrome A.

Mitofusin modulatory peptides are described which may function as activators or inhibitors of mitochondrial fusion. The sequences and compositions comprising the sequences are useful for treating diseases or disorders associated with mitofusin 1 (Mfn1) and/or mitofusin 2 (Mfn2) and mitochondrial dysfunction. Methods of treatment, pharmaceutical formulations and methods of identifying compounds that mimic the activity of the peptides for use in screening assays are also described.